Celyad Oncology announces the publication of the preclinical and clinical data of CYAD-211 providing proof-of-concept of its miRNA-based shRNA platform
Celyad Oncology has published preclinical and clinical data for CYAD-211, their first allogeneic CAR T-cell therapy candidate, in the International Journal of Molecular Science. The study focused on patients with relapsed or refractory multiple myeloma.
The therapy utilizes a novel microRNA-based shRNA technology that interferes with CD3ζ expression in the T-cell receptor complex. Preclinical data demonstrated successful knockdown of CD3ζ and inhibition of TCR-mediated activation both in vitro and in vivo.
The Phase I IMMUNICY-1 clinical trial results showed an overall good safety profile with some clinical responses. Notably, no signs of graft-versus-host disease (GvHD) were observed, validating the technology's effectiveness in preventing this common complication. This non-gene edited approach offers advantages in implementation, safety, efficiency, and the ability to modulate multiple target genes simultaneously.
Celyad Oncology ha pubblicato dati preclinici e clinici per CYAD-211, il loro primo candidato alla terapia CAR T-cell allogenica, nell'International Journal of Molecular Science. Lo studio si è concentrato su pazienti con mieloma multiplo recidivato o refrattario.
La terapia utilizza una nuova tecnologia shRNA basata su microRNA che interferisce con l'espressione di CD3ζ nel complesso del recettore T-cell. I dati preclinici hanno dimostrato un'efficace riduzione di CD3ζ e un'inibizione dell'attivazione mediata dal TCR sia in vitro che in vivo.
I risultati della fase I del trial clinico IMMUNICY-1 hanno mostrato un profilo di sicurezza complessivo buono con alcune risposte cliniche. In particolare, non sono stati osservati segni di malattia da trapianto contro ospite (GvHD), convalidando l'efficacia della tecnologia nel prevenire questa comune complicazione. Questo approccio non modificato geneticamente offre vantaggi in termini di implementazione, sicurezza, efficienza e capacità di modulare simultaneamente più geni target.
Celyad Oncology ha publicado datos preclínicos y clínicos para CYAD-211, su primer candidato a terapia CAR T-cell alogénica, en el International Journal of Molecular Science. El estudio se centró en pacientes con mieloma múltiple en recaída o refractario.
La terapia utiliza una nueva tecnología shRNA basada en microRNA que interfiere con la expresión de CD3ζ en el complejo del receptor T-cell. Los datos preclínicos demostraron una reducción efectiva de CD3ζ y una inhibición de la activación mediada por TCR tanto in vitro como in vivo.
Los resultados del ensayo clínico de fase I IMMUNICY-1 mostraron un perfil de seguridad general bueno con algunas respuestas clínicas. En particular, no se observaron signos de enfermedad injerto contra huésped (GvHD), validando la efectividad de la tecnología para prevenir esta complicación común. Este enfoque no editado genéticamente ofrece ventajas en implementación, seguridad, eficiencia y la capacidad de modular múltiples genes diana simultáneamente.
Celyad Oncology는 CYAD-211에 대한 전임상 및 임상 데이터를 국제 분자 과학 저널에 발표했습니다. 이 연구는 재발성 또는 난치성 다발성 골수종 환자에 초점을 맞췄습니다.
이 요법은 T세포 수용체 복합체에서 CD3ζ 발현을 방해하는 새로운 microRNA 기반 shRNA 기술을 활용합니다. 전임상 데이터는 CD3ζ의 성공적인 감소와 in vitro 및 in vivo에서 TCR 매개 활성화 억제를 입증했습니다.
1상 IMMUNICY-1 임상 시험 결과는 일부 임상 반응과 함께 전반적으로 좋은 안전성 프로필을 보여주었습니다. 특히, 이식편대숙주병(GvHD)의 징후가 관찰되지 않아 이 일반적인 합병증을 예방하는 기술의 효과가 입증되었습니다. 이 비유전자 편집 접근법은 구현, 안전성, 효율성 및 여러 표적 유전자를 동시에 조절할 수 있는 장점을 제공합니다.
Celyad Oncology a publié des données précliniques et cliniques pour CYAD-211, leur premier candidat à la thérapie CAR T-cell allogénique, dans l'International Journal of Molecular Science. L'étude s'est concentrée sur des patients atteints de myélome multiple récurrent ou réfractaire.
La thérapie utilise une nouvelle technologie shRNA basée sur microARN qui interfère avec l'expression de CD3ζ dans le complexe du récepteur T-cell. Les données précliniques ont montré une réduction réussie de CD3ζ et une inhibition de l'activation médiée par le TCR à la fois in vitro et in vivo.
Les résultats de l'essai clinique de phase I IMMUNICY-1 ont montré un bon profil de sécurité global avec certaines réponses cliniques. Notamment, aucun signe de maladie du greffon contre l'hôte (GvHD) n'a été observé, validant l'efficacité de la technologie dans la prévention de cette complication courante. Cette approche non modifiée génétiquement offre des avantages en matière d'implémentation, de sécurité, d'efficacité et de capacité à moduler simultanément plusieurs gènes cibles.
Celyad Oncology hat präklinische und klinische Daten für CYAD-211, ihren ersten allogenen CAR-T-Zelltherapiekandidaten, im International Journal of Molecular Science veröffentlicht. Die Studie konzentrierte sich auf Patienten mit rezidiviertem oder refraktärem multiplem Myelom.
Die Therapie nutzt eine neuartige microRNA-basierte shRNA-Technologie, die die CD3ζ-Expression im T-Zell-Rezeptor-Komplex beeinträchtigt. Präklinische Daten zeigten eine erfolgreiche Herabsetzung von CD3ζ und eine Hemmung der TCR-vermittelten Aktivierung sowohl in vitro als auch in vivo.
Die Ergebnisse der Phase-I-Studie IMMUNICY-1 zeigten ein insgesamt gutes Sicherheitsprofil mit einigen klinischen Reaktionen. Bemerkenswerterweise wurden keine Anzeichen einer Transplantat-gegen-Wirt-Erkrankung (GvHD) beobachtet, was die Wirksamkeit der Technologie zur Verhinderung dieser häufigen Komplikation bestätigt. Dieser nicht-genbearbeitete Ansatz bietet Vorteile in Bezug auf Implementierung, Sicherheit, Effizienz und die Fähigkeit, mehrere Zielgene gleichzeitig zu modulieren.
- First successful demonstration of non-gene edited allogeneic CAR T-cell therapy
- Good safety profile with no signs of graft-versus-host disease in clinical trials
- Technology proven effective in both preclinical and clinical settings
- Clinical responses observed in multiple myeloma patients
- Only 'some' clinical responses reported, suggesting efficacy
- Still in early Phase I trials, indicating long development timeline ahead
Insights
The publication of CYAD-211's preclinical and clinical data represents a significant milestone in allogeneic CAR T-cell therapy development. The successful demonstration of their miRNA-based shRNA platform's ability to create functional allogeneic CAR T-cells without gene editing is particularly noteworthy in the competitive cell therapy landscape.
The data reveals several critical achievements:
- Effective CD3ζ knockdown leading to TCR complex removal, which is essential for preventing graft-versus-host disease
- Clinical safety validation with no GvHD occurrences in multiple myeloma patients
- Demonstration of clinical responses while maintaining a favorable safety profile
The non-gene edited approach offers distinct advantages over current gene-editing technologies like CRISPR or TALENs. This method potentially reduces manufacturing complexity and associated costs while maintaining the ability to modulate multiple genes simultaneously. The platform's demonstrated safety and efficacy could position Celyad favorably in the rapidly evolving allogeneic cell therapy market.
For multiple myeloma treatment, where new therapeutic options are constantly needed, CYAD-211's BCMA-targeting approach aligns with proven successful strategies. The absence of GvHD in clinical trials is particularly significant, as this common complication has historically the broader application of allogeneic cell therapies.
This proof-of-concept validation could have broader implications beyond CYAD-211, potentially enabling the development of additional allogeneic CAR T-cell therapies using the same platform technology. The ability to tune and modulate multiple target genes simultaneously could prove valuable in addressing various hematological and solid tumors.
MONT-SAINT-GUIBERT,
Celyad Oncology (Euronext: CYAD) (Brussels:CYAD) (Paris:CYAD) (NASDAQ:CYAD) (the “Company”), today announces the publication of the preclinical data of the non-gene edited allogeneic CYAD-211 and clinical data from the Phase I IMMUNICY-1 clinical study which evaluated CYAD-211 in relapsed or refractory (r/r) multiple myeloma (MM) patients. The findings were published in the International Journal of Molecular Science (IJMS).
CYAD-211 is the Company’s first allogeneic chimeric antigen receptor (CAR) T-cell candidate, engineered to co-express a B-cell maturation antigen (BCMA)-specific CAR and a microRNA-based single shRNA which interferes with the expression of the CD3ζ component of the T-cell receptor (TCR) complex, evaluated clinically.
The IJMS publication includes preclinical data which showcases the knockdown of CD3ζ efficiently removed the TCR complex from the cell surface, and inhibited TCR mediated activation in vitro and in vivo. The publication also presents clinical data of the dose-escalation segment of the IMMUNICY-1 phase-I clinical trial (NCT04613557) in patients with r/r MM. Importantly, data highlighted an overall good safety profile and some clinical responses, with no signs of graft-versus-host disease (GvHD), demonstrating the effectiveness and safeness of the technology to abrogate the risk of GvHD.
Overall, these data provides the proof-of-concept of the safe administration of CAR T-cells engineered using a miRNA-based shRNA technology. CYAD-211 is the first allogeneic CAR T-cell candidate using a non-gene edited approach to achieve allogenicity. This differentiated strategy provides key advantages by being easily implemented, safe, efficient, tunable, and with the possibility to modulate multiple target genes simultaneously.
The publication will also be archived under “Scientific Publications” in the Science section of the Company’s website located at www.celyad.com.
About Celyad Oncology
Celyad Oncology is a cutting-edge biotechnology company dedicated to pioneering the discovery and advancement of revolutionary technologies for chimeric antigen receptor (CAR) T-cells. Its primary objective is to unlock the potential of its proprietary technology platforms and intellectual property, enabling to be at the forefront of developing next-generation CAR T-cell therapies. By fully leveraging its innovative technology platforms, Celyad Oncology aims to maximize the transformative impact of its candidate CAR T-cell therapies and redefine the future of CAR T-cell treatments. Celyad Oncology is based in Mont-Saint-Guibert,
Celyad Oncology Forward-Looking Statement
This release may contain forward-looking statements, including, without limitation, statements regarding beliefs about and expectations for the Company’s updated strategic business model, including associated potential benefits, transactions and partnerships, statements regarding the potential value of the Company’s IP, and statements regarding the continuation of the Company’s existence. The words “will,” “potential,” “continue,” “target,” “project,” “should” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this release are based on management’s current expectations and beliefs and are subject to a number of known and unknown risks, uncertainties and important factors which might cause actual events, results, financial condition, performance or achievements of Celyad Oncology to differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks related to the material uncertainty about the Company’s ability to continue as a going concern; the Company’s ability to realize the expected benefits of its updated strategic business model; the Company’s ability to develop its IP assets and enter into partnerships with outside parties; the Company’s ability to enforce its patents and other IP rights; the possibility that the Company may infringe on the patents or IP rights of others and be required to defend against patent or other IP rights suits; the possibility that the Company may not successfully defend itself against claims of patent infringement or other IP rights suits, which could result in substantial claims for damages against the Company; the possibility that the Company may become involved in lawsuits to protect or enforce its patents, which could be expensive, time-consuming, and unsuccessful; the Company’s ability to protect its IP rights throughout the world; the potential for patents held by the Company to be found invalid or unenforceable; and other risks identified in the latest Annual Report and subsequent filings and reports by Celyad Oncology. These forward-looking statements speak only as of the date of publication of this document and Celyad Oncology’s actual results may differ materially from those expressed or implied by these forward-looking statements. Celyad Oncology expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation.
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Investor & Media Contact:
David Georges, VP Finance and Administration
investors@celyad.com
Source: Celyad Oncology SA
FAQ
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