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

Rhea-AI Summary

Aprea Therapeutics announced that the Safety Review Committee (SRC) has approved dosing patients with ATRN-119 at 800 mg once daily in the ongoing ABOYA-119 clinical trial. ATRN-119, the first macrocyclic ATR inhibitor in clinic trials, has demonstrated a favorable safety profile through five dosage levels (up to 550 mg) with no dose-limiting toxicities. This advancement allows for Cohort 6 enrollment and positions Aprea to complete dose escalation and potentially release initial efficacy data by the second half of 2024. Clinical data show increasing systemic drug exposure with higher doses, and preliminary benefits observed in the trial include stable disease in two patients. The Phase 1 dose escalation is expected to conclude by the fourth quarter of 2024, with a recommended Phase 2 dosage to be identified by early 2025. Further Phase 2a cohort studies will begin in early 2025, aiming to evaluate ATRN-119's efficacy in advanced solid tumors with specific DDR pathway mutations.

Positive

• SRC approves 800 mg ATRN-119 dosing, advancing clinical trial.
• No dose-limiting toxicities at doses up to 550 mg, showcasing a favorable safety profile.
• Preliminary clinical benefits observed, including stable disease in two patients.
• Potential release of initial efficacy data in 2H 2024.
• Phase 1 dose escalation on track for completion by 4Q 2024.
• Anticipated identification of recommended Phase 2 dosage by 1Q 2025.
• Phase 2a cohort trials to begin in 1Q 2025, targeting advanced solid tumors with DDR mutations.

Negative

• No confirmed efficacy data yet, with initial results expected only in 2H 2024.
• Clinical benefits are preliminary, with only two patients showing stable disease.
• Phase 1 completion and Phase 2a trials still subject to future timelines, extending into 2025.
• Potential further cohorts (1100 mg, 1300 mg) indicate ongoing adjustments and unconfirmed dosing stability.

Insights

Financial Analyst

The endorsement by the Safety Review Committee (SRC) for dosing patients with ATRN-119 at 800 mg once daily in the ABOYA-119 clinical trial has notable financial implications. Aprea Therapeutics is demonstrating promising progress with its ATR inhibitor, potentially validating its development pipeline. The potential shift from Phase 1 to Phase 2a signifies a milestone that can attract additional investor interest and funding opportunities.

Key Points:

• Short-Term Implications: The progress in the clinical trial could lead to increased investor confidence, potentially boosting stock prices. Positive interim data, particularly safety profiles and stable disease results, usually reflect well on a company's market position.
• Long-Term Implications: If ATRN-119 shows significant efficacy in later-stage trials, it could lead to a new revenue stream upon FDA approval, addressing a high unmet medical need for cancers with DDR-related gene mutations. The market size for such targeted oncology treatments is substantial, potentially translating into significant long-term growth for Aprea.
• Industry Norms: It is common for biotech firms to experience stock volatility based on clinical trial progression. Investors should consider the inherent risks involved, as clinical trials for cancer treatments can be unpredictable.

Rating: 1 (Positive)

Oncology Doctor

The news from Aprea Therapeutics about the ABOYA-119 clinical trial provides important insights from a clinical perspective. The fact that ATRN-119 has been well tolerated up to 550 mg and that Cohort 6 can commence with 800 mg dosing is promising for both patients and clinicians.

Key Points:

• Tolerability and Dosage: The absence of dose-limiting toxicities (DLTs) is a significant achievement. It suggests that ATRN-119 might offer a more favorable safety profile compared to other ATR inhibitors, which can often have substantial side effects.
• Implications for Treatment: As ATR inhibitors target a clinically validated pathway, the effective dosage and tolerability could become important in treating cancers with DDR mutations. This progress is particularly significant given the high unmet medical need for effective therapies in this patient population.
• Future Prospects: The upcoming data from the Phase 2a cohort will be critical in determining the drug's efficacy. If successful, ATRN-119 could become a cornerstone in precision oncology treatments for patients with DDR-related gene mutations.

Rating: 1 (Positive)

Market Research Analyst

The advancement in Aprea Therapeutics' ATRN-119 clinical trial is a noteworthy development in the biopharmaceutical landscape. The broader context of this news can be framed within industry trends and market dynamics.

Key Points:

• Market Positioning: ATRN-119 is positioned as a first-in-class macrocyclic ATR inhibitor. This differentiation could provide Aprea Therapeutics a competitive edge in the oncology market, particularly if the drug continues to show a favorable safety and efficacy profile.
• Investor Sentiment: News of successful trial progress can drive positive sentiment among investors, particularly those focused on biotech and oncology sectors. Companies making strides in clinical trials often experience increased visibility and interest.
• Commercial Potential: The high unmet need for effective cancer therapies targeting DDR mutations signifies a substantial market opportunity. Success in later-phase trials could lead to significant commercial success, especially if ATRN-119 is the first approved drug in its class with a favorable safety profile.

Rating: 1 (Positive)

ATRN-119 is the first and only macrocyclic ATR inhibitor in the clinic, with best in class potential

On track to complete dose escalation in ABOYA-119 clinical trial and potentially generate initial human efficacy data in 2H 2024

Through the first 5 cohorts, ATRN-119 has been found to be safe and well tolerated with no dose limiting toxicities (DLTs) observed

DOYLESTOWN, Pa., May 28, 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 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).

“We are very pleased with the progress in the ABOYA-119 clinical trial and with the SRC’s recent endorsement to commence dosing of patients with ATRN-119 at 800 mg once daily representing progress in ATRN-119 development,” said Nadeem Q. Mirza, M.D., M.P.H., Chief Medical Officer of Aprea. “Pharmacokinetic data show that the duration of systemic exposure substantially increases with each dose level of ATRN-119. New data reported at the recent AACR annual meeting show that plasma concentrations of the drug are entering the expected therapeutic range at dose levels of 550 mg and above¹. We anticipate to announce additional safety and initial efficacy data from this study in the second half of 2024 and to complete dose escalation by the fourth quarter. Overall, we are very excited by ATRN-119, which we believe is differentiated from other ATR inhibitors in selectivity and toxicity profile.”

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. Part 1 (Phase 1) of the study is assessing tolerability, pharmacokinetics, recommended Phase 2 dose (RP2D) and analysis of patient biomarkers. At completion of Part 1, the company anticipates identification of a recommended Phase 2 dose that will be used in a Phase 2a cohort expansion (Part 2) to test the tolerability and potential efficacy of ATRN-119 monotherapy For more information, refer to please refer to clinicaltrials.gov NCT04905914. 

A total of 17 patients have been enrolled in the first five cohorts of the dose escalation stage (50 mg once daily, 100 mg once daily, 200 mg once daily, 350 mg once daily, and 550 mg once daily). Based on the safety profile, in March 2024 Aprea submitted an amendment to the FDA for the additional cohorts of 1100 mg and 1300 mg, with the goal of dosing patients in up to eight cohorts in total.

Preliminary signs of clinical benefit have been observed with two patients (data cutoff of March 12, 2024) achieving stable disease (SD) – one in the 50 mg once daily cohort and a second patient who showed longer duration when treated at 200 mg once daily. The latter patient at 200 mg once daily had SD at Days 55, 112, and 168. An update on the trial was featured in a poster at the AACR Annual Meeting this past April. For further details, including the status of all patients who were enrolled at that time, refer to the AACR poster on the Aprea corporate website here.

Initial efficacy data from Part 1 of the study may potentially be announced in 2H 2024. The Phase 1 dose escalation is expected to be completed in 4Q 2024, and RP2D is expected to be determined in 1Q 2025. Enrollment in the Phase 2a cohort is expected to begin in 1Q 2025 with additional safety and efficacy data expected in 3Q 2025.

ATRN-119 is a differentiated, potent and highly selective first-in-class macrocyclic inhibitor of ATR, a clinically validated target. It designed to be given to patients with mutations in DDR-related genes. Cancers with mutation in DDR-related genes represent a high unmet medical need and these patients have poor prognosis and, currently, have no approved effective therapies.

¹ A copy of the poster that features the pharmacokinetic data on ATRN-119 presented at the AACR Annual Meeting can be found on the Aprea corporate website here. The data demonstrate near dose proportional exposure following oral administration of ATRN-119 doses between 50 mg once daily to 550 mg once daily.

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. Aprea has completed all IND enabling studies for its oral, small molecule WEE1 inhibitor, APR-1051, and recently received FDA clearance of its IND. 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
Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statements for any reason, except as required by law.

Investor Contact:

Mike Moyer
LifeSci Advisors
mmoyer@lifesciadvisors.com

FAQ

What recent approval did Aprea Therapeutics receive for the ATRN-119 clinical trial?

The Safety Review Committee approved dosing patients with ATRN-119 at 800 mg once daily in the ongoing ABOYA-119 clinical trial.

What is the significance of ATRN-119 in clinical trials?

ATRN-119 is the first macrocyclic ATR inhibitor in clinical trials, demonstrating a favorable safety profile and potential efficacy in treating advanced solid tumors.

When is Aprea Therapeutics expected to release initial efficacy data for ATRN-119?

Initial efficacy data for ATRN-119 is expected to be released in the second half of 2024.

What are the preliminary results observed in the ABOYA-119 clinical trial?

Preliminary results show stable disease in two patients, one at 50 mg and another at 200 mg once daily.

What is the current status of the ABOYA-119 clinical trial's dose escalation phase?

The dose escalation phase is on track to be completed by the fourth quarter of 2024, with the recommended Phase 2 dosage to be determined by early 2025.