Zentalis Pharmaceuticals to Present Preclinical Azenosertib Data at ESMO 2024
Zentalis Pharmaceuticals (Nasdaq: ZNTL) will present preclinical data on its selective WEE1 inhibitor azenosertib at the ESMO 2024 Congress in Barcelona. The data shows synergistic anti-tumor effects when azenosertib is combined with topoisomerase I (TOP1) inhibitor-based antibody drug conjugates (ADCs).
Key findings include:
- Significant synergistic effects in all cell lines tested
- 50% complete tumor regression in HER2+ breast cancer models when combined with trastuzumab deruxtecan (T-Dxd)
- Notable combination effects in HER2+ ovarian and HER2-low breast cancer models
These results suggest azenosertib could improve responses to ADCs in advanced solid tumors by enhancing DNA damage and cell cycle deregulation.
Zentalis Pharmaceuticals (Nasdaq: ZNTL) presenterà dati preclinici sul suo inibitore selettivo WEE1 azenosertib al Congresso ESMO 2024 a Barcellona. I dati mostrano effetti anti-tumorali sinergici quando azenosertib è combinato con conjugati anticorpali a base di inibitori della topoisomerasi I (TOP1).
I principali risultati includono:
- Effetti sinergici significativi in tutte le linee cellulari testate
- Regressione tumorale completa del 50% nei modelli di cancro al seno HER2+ quando combinato con trastuzumab deruxtecan (T-Dxd)
- Effetti combinati notevoli nei modelli di cancro ovarico HER2+ e nei modelli di cancro al seno HER2-basso
Questi risultati suggeriscono che azenosertib potrebbe migliorare le risposte agli ADC nei tumori solidi avanzati aumentando i danni al DNA e la deregulation del ciclo cellulare.
Zentalis Pharmaceuticals (Nasdaq: ZNTL) presentará datos preclínicos sobre su inhibidor selectivo WEE1 azenosertib en el Congreso ESMO 2024 en Barcelona. Los datos muestran efectos anti-tumorales sinérgicos cuando azenosertib se combina con conjugados de fármacos anticuerpos basados en inhibidores de la topoisomerasa I (TOP1).
Los hallazgos clave incluyen:
- Efectos sinérgicos significativos en todas las líneas celulares probadas
- Regresión completa del tumor del 50% en modelos de cáncer de mama HER2+ cuando se combina con trastuzumab deruxtecan (T-Dxd)
- Efectos combinados notables en modelos de cáncer de ovario HER2+ y cáncer de mama HER2-bajo
Estos resultados sugieren que azenosertib podría mejorar las respuestas a los ADC en tumores sólidos avanzados al aumentar el daño al ADN y la desregulación del ciclo celular.
젠탈리스 제약(Zentalis Pharmaceuticals, Nasdaq: ZNTL)이 바르셀로나에서 열리는 ESMO 2024 Congress에서 선택적 WEE1 억제제 아제노세르티브(azenosertib)에 대한 전임상 데이터를 발표할 예정입니다. 데이터는 아제노세르티브가 톱이소머라제 I(TOP1) 억제제 기반 항체 약물 접합체(ADCs)와 결합할 때 시너지적 항종양 효과를 나타냅니다.
주요 발견 내용은 다음과 같습니다:
- 모든 세포주에서 상당한 시너지 효과
- 트라스투주맙 데룩세칸(T-Dxd)과 결합했을 때 HER2+ 유방암 모델에서 50%의 완전 종양 퇴축
- HER2+ 난소암 및 HER2-저유방암 모델에서 주목할 만한 조합 효과
이 결과는 아제노세르티브가 DNA 손상을 증가시키고 세포 주기 조절을 잘못되게 함으로써 진행된 고형 종양에서 ADC에 대한 반응을 개선할 수 있음을 시사합니다.
Zentalis Pharmaceuticals (Nasdaq: ZNTL) présentera des données précliniques sur son inhibiteur sélectif WEE1 azenosertib lors du Congrès ESMO 2024 à Barcelone. Les données montrent des effets anti-tumoraux synergiques lorsque azenosertib est combiné avec des conjugués anticorps-médicaments (ADCs) basés sur des inhibiteurs de la topoisomérase I (TOP1).
Les principaux résultats incluent :
- Effets synergiques significatifs dans toutes les lignées cellulaires testées
- Régression complète de 50 % des tumeurs dans des modèles de cancer du sein HER2+ lorsqu'il est combiné avec le trastuzumab deruxtecan (T-Dxd)
- Effets combinés notables dans des modèles de cancer ovarien HER2+ et de cancer du sein HER2-faible
Ces résultats suggèrent qu'azenosertib pourrait améliorer les réponses aux ADC dans les tumeurs solides avancées en augmentant les dommages à l'ADN et la dérégulation du cycle cellulaire.
Zentralis Pharmaceuticals (Nasdaq: ZNTL) wird präklinische Daten zu seinem selektiven WEE1-Inhibitor azenosertib auf dem ESMO 2024 Kongress in Barcelona präsentieren. Die Daten zeigen synergistische Antitumoreffekte, wenn azenosertib mit Antikörper-Wirkstoff-Konjugaten (ADCs), die auf Topoisomerase I (TOP1)-Inhibitoren basieren, kombiniert wird.
Wesentliche Ergebnisse beinhalten:
- Signifikante synergistische Effekte in allen getesteten Zelllinien
- 50% vollständige Tumorrückbildung in HER2+ Brustkrebsmodellen in Kombination mit Trastuzumab Deruxtecan (T-Dxd)
- Bemerkenswerte Kombinationseffekte in HER2+ Eierstock- und HER2-niedrigem Brustkrebsmodellen
Diese Ergebnisse legen nahe, dass azenosertib die Reaktionen auf ADCs bei fortgeschrittenen soliden Tumoren verbessern könnte, indem es DNA-Schäden und eine Deregulierung des Zellzyklus fördert.
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Azenosertib shows synergistic anti-tumor effects in combination with topoisomerase I (TOP1) inhibitor-based antibody drug conjugates
SAN DIEGO, Sept. 09, 2024 (GLOBE NEWSWIRE) -- Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, today announced that the company will present preclinical data from its selective WEE1 inhibitor azenosertib at the European Society of Medical Oncology (ESMO) 2024 Congress, occurring September 13-17 in Barcelona, Spain.
“The confluence of DNA damage induced by TOP1 inhibitors and cell cycle deregulation and genomic instability induced by azenosertib provides a mechanistic rationale for this combination, as well as more broadly with antibody drug conjugates (ADCs) utilizing these inhibitors as payloads,” said Mark Lackner, PhD, Chief Scientific Officer. “The preclinical data demonstrated this synergistic effect and suggest that azenosertib in combination with ADCs could be an important therapeutic approach in treating patients with advanced solid tumors.”
Presentation Details:
Poster #35P: The Selective WEE1 Inhibitor Azenosertib Shows Synergistic Antitumor Effects in Combination with Topoisomerase I Inhibitor-Based Antibody-Drug Conjugates
Presenter: Jianhui Ma, Zentalis Pharmaceuticals
Poster Display Date: Sunday, September 15, 2024
Data in the abstract showed that the combination of azenosertib with TOP1 inhibitors demonstrated significant synergistic effects in all cell lines tested. In HER2+ breast cancer animal models, those treated with the combination of azenosertib plus trastuzumab deruxtecan (T-Dxd) resulted in
About Azenosertib
Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.
About Zentalis Pharmaceuticals
Zentalis® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers. The Company’s lead product candidate, azenosertib (ZN-c3), is a potentially first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors and hematologic malignancies. Azenosertib is being evaluated as a monotherapy and in combination across multiple clinical trials and has broad franchise potential. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of its azenosertib clinical development program, the Company is exploring enrichment strategies targeting tumors of high genomic instability, such as Cyclin E1 positive tumors, homologous recombination deficient tumors and tumors with oncogenic driver mutations. The Company is also leveraging its extensive experience and capabilities across cancer biology and medicinal chemistry to advance its research on protein degraders. Zentalis has operations in San Diego.
For more information, please visit www.zentalis.com. Follow Zentalis on X/Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding the potential benefits of azenosertib in combination with ADCs as a therapeutic approach. The terms “could” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our ability to resolve the ongoing partial clinical hold on azenosertib; our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our plans, including the costs thereof, of development of any diagnostic tools; our substantial dependence on the success of our lead product candidate, azenosertib; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.
ZENTALIS® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release.
Contact:
Elizabeth Pingpank Hickin
ehickin@zentalis.com
860-463-0469
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