On October 16, 2023 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported highlights of two posters presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), October 14, 2023 in Boston, MA (Press release, Aprea, OCT 16, 2023, View Source [SID1234635988]). The data in the posters include first-in-human clinical data from the ongoing Phase 1 dose escalation trial of ATR inhibitor, ATRN-119 LINK to Poster, and pre-clinical data from the WEE1 inhibitor, ATRN-1051 LINK with planned IND submission Q4 2023.

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ATRN-119 is in an ongoing Phase 1/2a dose escalation trial in solid tumors to determine the recommended Phase 2 dose, with a daily dosing administration over a 56-day cycle. To date, no hematologic or liver function toxicities in these heavily pretreated solid tumor patients have been observed across the first three cohorts at dose levels of 50mg, 100mg, and 200mg (3 + 3 trial design) NCT04905914. The efficacy findings are still early in the dose escalation portion of the trial and there was one Stable Disease (SD) patient at the 50mg low dose cohort determined at end of cycle 1 (56-day cycle) (September 20, 2023 data cutoff). The company is actively enrolling cohort 4 at 350mg (subsequent 550mg cohort 5 and 800mg cohort 6 are planned) and anticipates dose expansion of the trial in Q2 2024.

The second poster presented focused on ATRN-1051, the WEE1 inhibitor, and highlights the selectivity of ATRN-1051 with low off-target activity against PLK1, PLK2 and PLK3, a family of kinases that promote M phase entry, a critical phase in the cell cycle. The selectivity of ATRN-1051 relative to the WEE1 class is also highlighted by its limited effects on red blood cell counts, hERG inhibition, and body weight loss in the pre-clinical data. PLK off-target activity has been a challenge for other WEE1 inhibitors in this class, as this off-target activity substantially counters the effects of WEE1 inhibition.

"We are excited to share the progress of our encouraging clinical and preclinical programs at this year’s AACR (Free AACR Whitepaper)-NCI-EORTC medical meeting," stated Dr. Oren Gilad, President and CEO of Aprea. "Based on the data to date, daily dosing of our ATR inhibitor, ATRN-119, appears to be well tolerated with a manageable toxicity profile, and no dose-limiting toxicities have been reported to date through data cutoff. We are currently enrolling patients in four US sites with the dose expansion cohort being on track to be initiated in 2Q 2024. The emerging tolerability profile presented in the poster may provide opportunities for potential combinations with multiple anti-cancer agents including our WEE1 inhibitor, ATRN-1051. This preclinical compound exhibits high potency for WEE1 inhibition in vitro and shows low off-target inhibition of the PLK family. The preclinical data findings and sensitivity to our WEE1 asset is guiding our clinical strategy and future patient selection. We look forward to advancing the drug to IND in the fourth quarter of this year."

Poster #1
Title: First in Human phase 1/2a trial of a macrocyclic ATR inhibitor (ATRN-119) in patients with advanced solid tumors
Abstract #: C034
Session: Session C; Level 2, Exhibit Hall D
Date/Time: Saturday, October 14 | 12:30pm – 4:00 pm ET
Presenter: Nadeem Q Mirza, M.D., M.P.H., Aprea Therapeutics, Inc.

Poster #2
Title: The DNA replication checkpoint inhibitors, ATRN-1051 (WEE1i) and ATRN-119 (ATRi), are potentially well-tolerated and effective cancer treatments
Abstract #: C147
Session: Session C; Level 2, Exhibit Hall D
Date/Time: Saturday, October 14 | 12:30pm – 4:00 pm ET
Presenter: Eric J. Brown, Ph.D., Perelman School of Medicine, University of Pennsylvania
*head-to-head comparisons have not been conducted