Aprea Therapeutics Announces Twice Daily (BID) Dosing of Patients in ABOYA-119 Clinical Trial of ATRN-119 to Potentially Optimize Clinical Outcomes and Strengthen Clinical Path Forward
Aprea Therapeutics (NASDAQ: APRE) has initiated twice daily (BID) dosing at 550mg in its ABOYA-119 Phase 1/2a clinical trial of ATRN-119, the first macrocyclic ATR inhibitor in clinical trials. The study, which previously tested once-daily doses from 50 to 800mg, now includes a protocol amendment for BID dosing starting at 550mg twice daily (1,100mg total daily dose).
The strategic shift to BID dosing aims to maintain optimal therapeutic levels over 24 hours, potentially enhancing efficacy and accelerating the path to regulatory approval. The trial continues to evaluate ATRN-119 as monotherapy in patients with advanced solid tumors having DNA damage response gene mutations. The Phase 1 readout is anticipated in the second half of 2025.
Aprea Therapeutics (NASDAQ: APRE) ha avviato la somministrazione due volte al giorno (BID) di 550mg nel suo studio clinico di fase 1/2a ABOYA-119 relativo all'ATRN-119, il primo inibitore macrociclico dell'ATR in sperimentazione clinica. Lo studio, che in precedenza aveva testato dosi giornaliere una sola volta da 50 a 800mg, ora include una modifica del protocollo per il dosaggio BID a partire da 550mg due volte al giorno (1.100mg di dose giornaliera totale).
Il passaggio strategico al dosaggio BID mira a mantenere livelli terapeutici ottimali per 24 ore, potenzialmente aumentando l'efficacia e accelerando il percorso verso l'approvazione regolatoria. Lo studio continua a valutare l'ATRN-119 come monoterapia in pazienti con tumori solidi avanzati che presentano mutazioni nei geni della risposta al danno del DNA. I risultati della fase 1 sono attesi nella seconda metà del 2025.
Aprea Therapeutics (NASDAQ: APRE) ha iniciado la administración dos veces al día (BID) de 550mg en su ensayo clínico de fase 1/2a ABOYA-119 de ATRN-119, el primer inhibidor macro cíclico de ATR en ensayos clínicos. El estudio, que anteriormente probó dosis una vez al día de 50 a 800mg, ahora incluye una modificación del protocolo para la dosificación BID comenzando en 550mg dos veces al día (1,100mg de dosis diaria total).
El cambio estratégico a la dosificación BID tiene como objetivo mantener niveles terapéuticos óptimos durante 24 horas, lo que podría mejorar la eficacia y acelerar el camino hacia la aprobación regulatoria. El ensayo sigue evaluando ATRN-119 como monoterapia en pacientes con tumores sólidos avanzados que tienen mutaciones en los genes de respuesta al daño del ADN. Se anticipa que los resultados de la fase 1 se presenten en la segunda mitad de 2025.
Aprea Therapeutics (NASDAQ: APRE)는 ATRN-119에 대한 ABOYA-119 1/2a 임상 시험에서 하루 두 번(BID) 550mg 투여를 시작했습니다. ATR의 매크로사이클 억제제입니다. 이 연구는 이전에 50mg에서 800mg까지의 하루 한 번 투여를 테스트했으며, 이제 550mg 하루 두 번 투여(BID)를 위한 프로토콜 수정이 포함되어 있습니다 (총 일일 복용량 1,100mg).
BID 투여로의 전략적 전환은 24시간 동안 최적의 치료 수준을 유지하여 효능을 높이고 규제 승인을 가속화하는 것을 목표로 합니다. 이 시험은 DNA 손상 반응 유전자 돌연변이를 가진 진행성 고형 종양 환자에서 ATRN-119를 단일요법으로 평가하는 것을 계속하고 있습니다. 1상 결과는 2025년 하반기에 발표될 것으로 예상됩니다.
Aprea Therapeutics (NASDAQ: APRE) a lancé un schéma posologique deux fois par jour (BID) de 550 mg dans son essai clinique de phase 1/2a ABOYA-119 concernant l'ATRN-119, le premier inhibiteur ATR macrocyclique en essais cliniques. L'étude, qui avait précédemment testé des doses une fois par jour allant de 50 à 800 mg, inclut désormais une modification du protocole pour une posologie BID à partir de 550 mg deux fois par jour (1 100 mg de dose quotidienne totale).
Le changement stratégique vers une posologie BID vise à maintenir des niveaux thérapeutiques optimaux sur 24 heures, ce qui pourrait améliorer l'efficacité et accélérer le passage vers l'approbation réglementaire. L'essai continue d'évaluer l'ATRN-119 comme monothérapie chez des patients atteints de tumeurs solides avancées ayant des mutations dans les gènes de réponse aux dommages de l'ADN. Les résultats de la phase 1 sont attendus dans la seconde moitié de 2025.
Aprea Therapeutics (NASDAQ: APRE) hat mit einer zweimal täglichen (BID) Dosierung von 550mg in seiner ABOYA-119 Phase 1/2a klinischen Studie zu ATRN-119, dem ersten makrozyklischen ATR-Inhibitor in klinischen Studien, begonnen. Die Studie, die zuvor einmal täglich Dosen von 50 bis 800mg getestet hatte, beinhaltet nun eine Protokolländerung für die BID-Dosierung, beginnend mit 550mg zweimal täglich (1.100mg Gesamtdosis pro Tag).
Der strategische Wechsel zur BID-Dosierung zielt darauf ab, optimale therapeutische Werte über 24 Stunden aufrechtzuerhalten, was die Wirksamkeit erhöhen und den Weg zur behördlichen Genehmigung beschleunigen könnte. Die Studie bewertet weiterhin ATRN-119 als Monotherapie bei Patienten mit fortgeschrittenen soliden Tumoren mit Mutationen in Genen der DNA-Schadenreaktion. Die Ergebnisse der Phase 1 werden in der zweiten Jahreshälfte 2025 erwartet.
- First macrocyclic ATR inhibitor to enter clinical trials
- Only ATR inhibitor being tested as monotherapy on continuous twice daily schedule
- Protocol amendment allows for potential optimization of therapeutic levels
- Trial continues both once-daily and twice-daily dosing schedules independently
- Phase 1 results not expected until second half of 2025
- Multiple dosing regimens may extend trial duration and increase costs
Insights
The shift to twice-daily dosing of ATRN-119 represents a significant optimization in the drug's development strategy. The 550mg BID dosing (total
The concurrent evaluation of both once-daily and twice-daily dosing schedules provides flexibility in determining the optimal regimen. While this modification may extend the development timeline, with Phase 1 results now expected in H2 2025, it potentially reduces clinical development risk by addressing pharmacodynamic considerations early. The focus on monotherapy in DDR-mutated tumors, combined with optimized dosing, could differentiate ATRN-119 in the competitive ATR inhibitor landscape.
For a micro-cap company with a market cap of just
However, investors should note that this timeline adjustment means a longer runway to meaningful clinical data and potential catalysts. The company's emphasis on partnership opportunities suggests a focus on securing additional resources or strategic alternatives, which may be important given its current market capitalization and the typically high costs of clinical development.
Twice daily (BID) dosing regimen expected to maximize clinical benefit for patients by optimizing the activity of Aprea’s experimental drug, ATRN-119, over a 24-hour daily cycle
New regimen potentially optimizes clinical outcomes and strengthens the clinical path forward
ATRN-119 is the first macrocyclic ATR inhibitor to enter clinical trials
DOYLESTOWN, Pa., Dec. 11, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage precision oncology company developing innovative therapies for cancers with specific genetic alterations to potentially minimize damage to healthy cells, announced today that the first patient has been dosed at Dose Level 7, evaluating ATRN-119 550 mg twice daily, in the ongoing ABOYA-119 Phase 1/2a clinical trial.
The ABOYA-119 trial is evaluating ATRN-119 as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DNA damage response (DDR)-related genes. The study was initially designed to dose patients with ATRN-119 once daily and has tested doses of 50 to 800 mg to date. A protocol amendment allows for twice daily dosing, beginning with 550 mg twice daily (for a total daily dose of 1,100 mg). This strategic dose adjustment is driven by robust scientific evidence suggesting that more frequent dosing of ATRN-119 will maintain optimal therapeutic levels and potentially enhance the drug’s efficacy.
Twice daily dosing is expected to optimize ATRN-119’s activity across a 24-hour cycle thereby providing better target coverage and maximal benefit. This will increase the likelihood of achieving superior clinical outcomes and may potentially accelerate the path to regulatory approval and commercialization. It could also strengthen Aprea’s competitive positioning by addressing key pharmacokinetic and pharmacodynamic factors.
“The addition of twice daily dosing in the ABOYA-119 trial underscores Aprea’s commitment to delivering innovative treatments while continuously refining our approach based on the latest data and insights,” said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. “Twice daily dosing represents a proactive step to de-risk the trial, potentially increasing the probability of success. Importantly, it reflects our commitment to scientific excellence and we believe it positions the ATRN-119 program as a high-value asset that may be differentiated from other ATR inhibitors. To our knowledge, we believe ATRN-119 is the only ATR inhibitor in clinical development that is currently being tested as monotherapy on a continuous twice daily schedule. We believe this adjustment will further enhance shareholder value and support the long-term success of our mission.”
Dr. Gilad added, “This approach not only enhances our development strategy but also creates new opportunities for partnership that could accelerate commercialization of ATRN-119 and expand patient access globally.”
Anthony Tolcher, M.D., FRCPC, FACP, CEO of NEXT Oncology and Investigator in the ABOYA-119 trial commented, “Inhibition of ATR has emerged as a promising strategy for cancer treatment that exploits synthetic lethal interactions with proteins that are involved in DNA damage repair. This mechanism holds considerable promise for patients with difficult-to-treat cancers. We are pleased to continue to enroll our patients in this important study and recognize that a twice daily dosing regimen of ATRN-119 may allow us to maximize the therapeutic potential of the drug.”
Dose escalation in the ABOYA-119 trial is expected to continue with both once-daily and the twice-daily dosing schedules, to be studied independently. The primary endpoint of the trial is the tolerability and pharmacokinetics of ATRN-119. Under the current updated protocol, Aprea anticipates the Phase 1 readout in the second half of 2025. For more information, please refer to clinicaltrials.gov NCT04905914.
About ATRN-119
ATRN-119 is a potent and highly selective first-in-class macrocyclic ATR inhibitor, designed to be used in patients with mutations in DDR-related genes. Cancers with mutations in DDR-related genes represent a high unmet medical need. Patients with DDR-related gene mutations have a poor prognosis and, currently, there are no effective therapies available for them.
About Aprea
Aprea is pioneering a new approach to treat cancer by exploiting vulnerabilities associated with cancer cell mutations. This approach was developed to kill tumors but to minimize the effect on normal, healthy cells, decreasing the risk of toxicity that is frequently associated with chemotherapy and other treatments. Aprea’s technology has potential applications across multiple cancer types, enabling it to target a range of tumors, including ovarian, colorectal, prostate, and breast cancers. The company’s lead programs are APR-1051, an oral, small-molecule inhibitor of WEE1 kinase, and ATRN-119, a small molecule ATR inhibitor, both in clinical development for solid tumor indications. For more information, please visit the company website at www.aprea.com, and follow us on LinkedIn, or X.
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 and Media Contact:
Mike Moyer
LifeSci Advisors
mmoyer@lifesciadvisors.com
FAQ
What is the new dosing schedule for ATRN-119 in Aprea's ABOYA-119 trial?
When will Aprea (APRE) release Phase 1 results for the ABOYA-119 trial?
What makes ATRN-119 unique among ATR inhibitors in clinical development?
What patient population is being targeted in Aprea's ABOYA-119 trial?
What are the primary endpoints of Aprea's ABOYA-119 trial?
