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Actuate Announces Scientific Reports Publication on Elraglusib’s Novel Immunomodulatory Mechanism of Action as a GSK-3β Inhibitor

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Actuate Therapeutics (NASDAQ: ACTU) has announced the publication of novel mechanistic data for its development candidate, elraglusib, in Scientific Reports. The study, titled "Targeted inhibition of glycogen synthase kinase‑3 using 9‑ING‑41 (elraglusib) enhances CD8 T‑cell‑reactivity against neuroblastoma cells," reveals elraglusib's potential as an immune modulator in neuroblastoma treatment.

Key findings include:

  • Elraglusib enhances MHC-I molecule surface expression on neuroblastoma cells
  • It disrupts NK-κB signaling, promoting cancer cell apoptosis
  • Boosts IFNγ signaling through the JAK/STAT pathway
  • When combined with anti-PD-1 treatment, it enhances CD8+ T cell proliferation and activation

These insights suggest elraglusib's potential to activate the immune system in cancers previously unresponsive to checkpoint inhibitors. Elraglusib is currently in Phase 2 trials for metastatic pancreatic cancer and Phase 1/2 trials for Ewing Sarcoma and related sarcomas.

Actuate Therapeutics (NASDAQ: ACTU) ha annunciato la pubblicazione di nuovi dati meccanistici per il suo candidato terapeutico, elraglusib, su Scientific Reports. Lo studio, intitolato "L'inibizione mirata della glicogeno sintetasi chinasi-3 mediante 9-ING-41 (elraglusib) aumenta la reattività dei linfociti T CD8 contro le cellule di neuroblastoma," rivela il potenziale di elraglusib come modulatore immunitario nel trattamento del neuroblastoma.

I principali risultati includono:

  • Elraglusib aumenta l'espressione della superficie delle molecole MHC-I sulle cellule di neuroblastoma
  • Disruzione della segnalazione NK-κB, promuovendo l'apoptosi delle cellule cancerose
  • Aumento della segnalazione di IFNγ attraverso la via JAK/STAT
  • Quando combinato con il trattamento anti-PD-1, migliora la proliferazione e l'attivazione delle cellule T CD8+

Queste intuizioni suggeriscono il potenziale di elraglusib per attivare il sistema immunitario in tumori precedentemente non responsivi agli inibitori dei checkpoint. Elraglusib è attualmente in fase 2 di sperimentazione clinica per il cancro pancreatico metastatico e in fase 1/2 per il sarcoma di Ewing e sarcomi correlati.

Actuate Therapeutics (NASDAQ: ACTU) ha anunciado la publicación de nuevos datos mecanicistas para su candidato de desarrollo, elraglusib, en Scientific Reports. El estudio, titulado "Inhibición dirigida de la glucógeno sintasa quinasa-3 utilizando 9-ING-41 (elraglusib) mejora la reactividad de células T CD8 contra células de neuroblastoma," revela el potencial de elraglusib como modulador inmunológico en el tratamiento del neuroblastoma.

Las principales conclusiones incluyen:

  • Elraglusib mejora la expresión en la superficie de las moléculas MHC-I en células de neuroblastoma
  • Interfiere con la señalización de NK-κB, promoviendo la apoptosis de células cancerosas
  • Estimula la señalización de IFNγ a través de la vía JAK/STAT
  • Cuando se combina con tratamiento anti-PD-1, aumenta la proliferación y activación de células T CD8+

Estas ideas sugieren el potencial de elraglusib para activar el sistema inmunológico en cánceres que previamente no respondían a los inhibidores de puntos de control. Elraglusib está actualmente en ensayos de fase 2 para el cáncer pancreático metastásico y en ensayos de fase 1/2 para el sarcoma de Ewing y sarcomas relacionados.

액추에이트 제약 (NASDAQ: ACTU)은 개발 후보 물질인 엘라글루시브에 대한 새로운 기전 데이터를 Scientific Reports에 발표했다고 밝혔습니다. "9-ING-41 (엘라글루시브)을 이용한 글리코겐 합성효소 키나제-3의 타겟 억제가 신경 모세포종 세포에 대한 CD8 T세포 반응성을 향상시킨다"는 제목의 이 연구는 신경 모세포종 치료에 있어 면역 조절제로서의 엘라글루시브의 잠재력을 드러냅니다.

주요 결과는 다음과 같습니다:

  • 엘라글루시브는 신경 모세포종 세포에서 MHC-I 분자의 표면 발현을 향상시킵니다
  • NK-κB 신호 전달을 방해하여 암세포의 세포사를 촉진합니다
  • JAK/STAT 경로를 통한 IFNγ 신호 전달을 향상시킵니다
  • 항-PD-1 치료와 함께 사용할 때, CD8+ T 세포의 증식 및 활성화를 향상시킵니다

이러한 통찰력은 엘라글루시브가 체크포인트 억제제에 반응하지 않았던 암에서 면역 체계를 활성화할 가능성이 있음을 시사합니다. 엘라글루시브는 현재 전이성 췌장암에 대한 2상 시험과 유잉 육종 및 관련 육종에 대한 1/2상 시험 중입니다.

Actuate Therapeutics (NASDAQ: ACTU) a annoncé la publication de nouvelles données mécanistes pour son candidat de développement, elraglusib, dans Scientific Reports. L'étude, intitulée "Inhibition ciblée de la glycogène synthase kinase-3 utilisant 9-ING-41 (elraglusib) améliore la réactivité des cellules T CD8 contre les cellules de neuroblastome," révèle le potentiel d'elraglusib en tant que modulateur immunitaire dans le traitement du neuroblastome.

Les principales conclusions incluent :

  • Elraglusib augmente l'expression des molécules MHC-I à la surface des cellules de neuroblastome
  • Il perturbe la signalisation NK-κB, favorisant l'apoptose des cellules cancéreuses
  • Augmente la signalisation de l'IFNγ via la voie JAK/STAT
  • Lorsqu'il est combiné avec un traitement anti-PD-1, il améliore la prolifération et l'activation des cellules T CD8+

Ces révélations suggèrent le potentiel d'elraglusib à activer le système immunitaire dans des cancers qui étaient auparavant non réceptifs aux inhibiteurs de points de contrôle. Elraglusib est actuellement en essais de phase 2 pour le cancer du pancréas métastatique et en essais de phase 1/2 pour le sarcome d'Ewing et des sarcomes apparentés.

Actuate Therapeutics (NASDAQ: ACTU) hat die Veröffentlichung neuer mechanistischer Daten für seinen Entwicklungskandidaten elraglusib in Scientific Reports angekündigt. Die Studie mit dem Titel „Gezielte Hemmung der Glykogensynthase-Kinase-3 durch 9-ING-41 (elraglusib) verbessert die Reaktivität von CD8-T-Zellen gegen Neuroblastomzellen“ zeigt das Potenzial von elraglusib als Immunmodulator bei der Behandlung von Neuroblastomen.

Wichtige Erkenntnisse umfassen:

  • Elraglusib erhöht die Oberflächenexpression von MHC-I-Molekülen auf Neuroblastomzellen
  • Es stört die NK-κB-Signalübertragung und fördert den programmierten Zelltod von Krebszellen
  • Steigert die IFNγ-Signalgebung über den JAK/STAT-Weg
  • Bei Kombination mit einer anti-PD-1-Behandlung verbessert es die Proliferation und Aktivierung von CD8+ T-Zellen

Diese Erkenntnisse deuten darauf hin, dass elraglusib das Potenzial hat, das Immunsystem bei Krebs zu aktivieren, das zuvor nicht auf Checkpoint-Inhibitoren angesprochen hat. Elraglusib befindet sich derzeit in Phase-2-Studien bei metastasiertem Pankreaskrebs und in Phase-1/2-Studien bei Ewing-Sarkom und verwandten Sarkomen.

Positive
  • Publication of novel mechanistic data for elraglusib in Scientific Reports
  • Elraglusib shows potential to enhance immune system activation in cancers unresponsive to checkpoint inhibitors
  • Ongoing Phase 2 trial for metastatic pancreatic cancer
  • Ongoing Phase 1/2 trial for Ewing Sarcoma and related sarcomas
Negative
  • None.
  • New Mechanistic Insights Underscore Multiple Potential Roles for Elraglusib as an Immune Modulator in the treatment of Neuroblastoma
  • Study Illustrates Potential to Activate the Immune System Even in Cancers That Have Not Previously Responded to Checkpoint Inhibitors

CHICAGO and FORT WORTH, Texas, Sept. 23, 2024 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company, focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), announced the Scientific Reports publication of novel mechanistic data for its development candidate, elraglusib.

The article, entitled, “Targeted inhibition of glycogen synthase kinase3 using 9ING41 (elraglusib) enhances CD8 Tcellreactivity against neuroblastoma cells” is available online.

“The mechanistic data published in Scientific Reports provides crucial evidence of elraglusib’s ability to enhance activation of the immune system by tumor cells,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “By improving antigen presentation and enhancing the activation of CD8+ cytotoxic T cells, we are paving the way for more effective immunotherapeutic strategies including combinations of elraglusib with checkpoint inhibitors.” Using neuroblastoma, which is typically refractory to checkpoint inhibitors, as a model system, these findings illustrate the potential to activate the immune system even in cancers that have not previously responded to checkpoint inhibitors and underscore elraglusib’s potential as a highly innovative treatment for challenging cancers.

The summary of key mechanistic findings:

  • Elraglusib significantly enhances MHC-I molecule surface expression of neuroblastoma cells, improving their recognition by cytotoxic T lymphocytes (CTLs)
  • Treatment with elraglusib leads to the disruption of NK-κB signaling, a key contributor to tumor cell survival, promoting cancer cell apoptosis and reducing treatment resistance
  • Elraglusib boosts IFNγ signaling through the JAK/STAT pathway, particularly STAT1, which further supports improved antigen presentation and immune response
  • When combined with an anti-PD-1 treatment, elraglusib boosted CD8+ T cell proliferation and activation by neuroblastoma cells, showing potential for further development of these tumor immune response enhancing therapeutics.

“Despite the clinical benefit observed with checkpoint inhibitors in many advanced cancer types, the majority of patients treated with checkpoint inhibitors fail to respond,” said Dr. Andrew Mazar, Actuate’s Scientific Co-founder and Chief Operating Officer. “The ability to enhance immunogenicity in a tumor such as neuroblastoma that is not unrecognized by the immune system, holds therapeutic promise for neuroblastoma patients and could potentially be translated for the treatment of other immunologically cold tumors as well.”

Elraglusib is currently being evaluated in Phase 2 Trial in metastatic pancreatic cancer (NCT03678883) and Phase 1/2 Trial (NCT04239092) in Ewing Sarcoma (EWS) and EWS-related sarcomas.

About Actuate Therapeutics, Inc.

Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers. Actuate’s lead investigational drug product, elraglusib (a novel GSK-3β inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy including EMT, NF-kB-mediated resistance and several DDR pathways. Elraglusib also acts as a mediator of anti-tumor immunity through the inhibition of NF-kB in immune cells and regulates multiple immune checkpoints and immune cell function. For additional information, please visit the Company’s website at http://www.actuatetherapeutics.com.

Forward-Looking Statements

This press release contains forward-looking statements about us, including our clinical trials and development plans, and our industry. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements related to present facts or current conditions or of historical facts, contained in this press release are forward-looking statements. Accordingly, these statements involve estimates, assumptions, substantial risks and uncertainties which could cause actual results to differ materially from those expressed in them, including but not limited to that clinical and preclinical drug development involves a lengthy and expensive process with uncertain timelines and outcomes, results of prior preclinical studies and early clinical trials are not necessarily predictive of future results, and elraglusib may not achieve favorable results in clinical trials or preclinical studies or receive regulatory approval on a timely basis, if at all; that we may not successfully enroll additional patients or establish or advance plans for further development; that elraglusib could be associated with side effects, adverse events or other properties or safety risks, which could delay or preclude regulatory approval, cause us to suspend or discontinue clinical trials or result in other negative consequences; our reliance on third parties to conduct our non-clinical studies and our clinical trials; our reliance on third-party licensors and ability to preserve and protect our intellectual property rights; that we face significant competition from other biotechnology and pharmaceutical companies; and our ability to fund development activities. In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading “Risk Factors” in our final prospectus filed with the SEC on August 13, 2024 pursuant to Rule 424(b)(4) under the Securities Act with respect to our Registration Statement on Form S-1 (File No. 333-279734) and other filings with the SEC. Because the risk factors referred to above could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements made by us or on our behalf, you should not place undue reliance on any forward-looking statements. Further, any forward-looking statement speaks only as of the date on which it is made. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Unless legally required, we do not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events.

Investor Contact

Mike Moyer

Managing Director

LifeSci Advisors, LLC

mmoyer@lifesciadvisors.com


FAQ

What is the mechanism of action of elraglusib according to the Scientific Reports publication?

According to the publication, elraglusib enhances MHC-I molecule surface expression on neuroblastoma cells, disrupts NK-κB signaling, boosts IFNγ signaling through the JAK/STAT pathway, and when combined with anti-PD-1 treatment, enhances CD8+ T cell proliferation and activation.

What potential does elraglusib show for treating neuroblastoma according to the Actuate Therapeutics (ACTU) study?

The study suggests that elraglusib has the potential to activate the immune system in neuroblastoma, which is typically refractory to checkpoint inhibitors. This indicates promise for treating neuroblastoma and potentially other immunologically cold tumors.

What clinical trials is Actuate Therapeutics (ACTU) currently conducting for elraglusib?

Actuate Therapeutics is currently evaluating elraglusib in a Phase 2 trial for metastatic pancreatic cancer (NCT03678883) and a Phase 1/2 trial (NCT04239092) for Ewing Sarcoma (EWS) and EWS-related sarcomas.

How does elraglusib potentially enhance the effectiveness of checkpoint inhibitors according to the Actuate Therapeutics (ACTU) study?

The study shows that elraglusib, when combined with an anti-PD-1 treatment, boosted CD8+ T cell proliferation and activation by neuroblastoma cells. This suggests potential for enhancing the effectiveness of checkpoint inhibitors in tumors that are typically unresponsive to such treatments.

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