On May 28, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported 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 (Press release, Aprea, MAY 28, 2024, View Source [SID1234643727]). This decision follows review of the safety and pharmacokinetic data from patients treated at 550 mg once daily (Cohort 5).

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"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 (Free AACR Whitepaper) 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 (Free AACR Whitepaper) Annual Meeting this past April. For further details, including the status of all patients who were enrolled at that time, refer to the AACR (Free AACR Whitepaper) 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 (Free AACR Whitepaper) 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.