Exscientia to Present New Preclinical Data for AI-designed LSD1 and MALT1 Inhibitors at ENA 2024
Exscientia plc (Nasdaq: EXAI) announced three abstracts to be presented at the 36th EORTC-NCI-AACR (ENA) Symposium 2024 in Barcelona, Spain. The presentations focus on:
1. Combining MALT1 inhibitor EXS73565 with BTK inhibitors for enhanced efficacy in B-cell malignancies.
2. In vivo studies of EXS74539, a novel LSD1 inhibitor for acute myeloid leukemia (AML).
3. Xcellomics collaboration with the University of Oxford for rapid translation of high-throughput screening results.
Key highlights include:
- EXS73565 combined with zanubrutinib showed deeper, more durable efficacy in B-cell malignancy models.
- EXS74539 demonstrated platelet level effects in AML models.
- Identification of 12 potential pharmacodynamic biomarkers for LSD1 inhibitor activity.
- Both EXS73565 and EXS74539 are expected to enter clinical studies in early 2025.
Exscientia plc (Nasdaq: EXAI) ha annunciato tre abstract che saranno presentati al 36° Simposio EORTC-NCI-AACR (ENA) 2024 a Barcellona, Spagna. Le presentazioni si concentrano su:
1. La combinazione dell'inibitore MALT1 EXS73565 con inibitori BTK per una maggiore efficacia nelle neoplasie delle cellule B.
2. Studi in vivo di EXS74539, un nuovo inibitore LSD1 per la leucemia mieloide acuta (AML).
3. Collaborazione con Xcellomics e l'Università di Oxford per la rapida traduzione dei risultati dello screening ad alta capacità.
I principali punti salienti includono:
- EXS73565 combinato con zanubrutinib ha mostrato un'efficacia più profonda e duratura nei modelli di neoplasia delle cellule B.
- EXS74539 ha dimostrato effetti a livello piastrinico nei modelli di AML.
- Identificazione di 12 potenziali biomarcatori farmacodinamici per l'attività degli inibitori LSD1.
- Sia EXS73565 che EXS74539 dovrebbero entrare in studi clinici all'inizio del 2025.
Exscientia plc (Nasdaq: EXAI) anunció tres resúmenes que se presentarán en el 36º Simposio EORTC-NCI-AACR (ENA) 2024 en Barcelona, España. Las presentaciones se enfocan en:
1. La combinación del inhibidor MALT1 EXS73565 con inhibidores BTK para una mayor eficacia en las malignidades de células B.
2. Estudios in vivo de EXS74539, un nuevo inhibidor de LSD1 para la leucemia mieloide aguda (LMA).
3. Colaboración con Xcellomics y la Universidad de Oxford para la rápida traducción de resultados de cribado de alto rendimiento.
Los aspectos clave incluyen:
- EXS73565 combinado con zanubrutinib mostró una eficacia más profunda y duradera en modelos de malignidad de células B.
- EXS74539 demostró efectos a nivel plaquetario en modelos de LMA.
- Identificación de 12 posibles biomarcadores farmacodinámicos para la actividad de inhibidores de LSD1.
- Tanto EXS73565 como EXS74539 se espera que ingresen en estudios clínicos a principios de 2025.
Exscientia plc (Nasdaq: EXAI)는 2024년 스페인 바르셀로나에서 열리는 제36회 EORTC-NCI-AACR(ENA) 심포지엄에서 발표될 세 가지 초록을 발표했습니다. 발표 내용은 다음과 같습니다:
1. B세포 악성종양에서의 효능 향상을 위한 MALT1 억제제 EXS73565와 BTK 억제제의 결합.
2. 급성 골수성 백혈병(AML)을 위한 새로운 LSD1 억제제 EXS74539의 생체 내 연구.
3. 고처리량 스크리닝 결과의 빠른 전환을 위한 옥스포드 대학교와 Xcellomics의 협력.
주요 하이라이트는 다음과 같습니다:
- EXS73565와 자누브루티닙의 조합은 B세포 악성종양 모델에서 더 깊고 지속적인 효능을 나타냈습니다.
- EXS74539는 AML 모델에서 혈소판 수준의 효과를 보였습니다.
- LSD1 억제제 활성을 위한 12개의 잠재적 약리역학 바이오마커가 확인되었습니다.
- EXS73565와 EXS74539 모두 2025년 초에 임상 연구에 진입할 것으로 예상됩니다.
Exscientia plc (Nasdaq: EXAI) a annoncé trois résumés qui seront présentés lors du 36ème Symposium EORTC-NCI-AACR (ENA) 2024 à Barcelone, en Espagne. Les présentations se concentrent sur :
1. La combinaison de l'inhibiteur MALT1 EXS73565 avec des inhibiteurs de BTK pour une efficacité accrue dans les malignités des cellules B.
2. Études in vivo d'EXS74539, un nouvel inhibiteur de LSD1 pour la leucémie myéloïde aiguë (LMA).
3. Collaboration avec Xcellomics et l'Université d'Oxford pour la traduction rapide des résultats de criblage à haut débit.
Les points clés incluent :
- EXS73565 combiné avec le zanubrutinib a montré une efficacité plus profonde et plus durable dans les modèles de malignité des cellules B.
- EXS74539 a démontré des effets au niveau des plaquettes dans des modèles de LMA.
- Identification de 12 biomarqueurs pharmacodynamiques potentiels pour l'activité des inhibiteurs de LSD1.
- EXS73565 et EXS74539 devraient entrer dans des études cliniques début 2025.
Exscientia plc (Nasdaq: EXAI) hat drei Abstracts angekündigt, die auf dem 36. EORTC-NCI-AACR (ENA) Symposium 2024 in Barcelona, Spanien, präsentiert werden. Die Präsentationen konzentrieren sich auf:
1. Die Kombination des MALT1-Inhibitors EXS73565 mit BTK-Inhibitoren zur Verbesserung der Wirksamkeit bei B-Zell-Malignomen.
2. In-vivo-Studien zu EXS74539, einem neuartigen LSD1-Inhibitor für die akute myeloische Leukämie (AML).
3. Kooperation mit Xcellomics und der Universität Oxford zur schnellen Umsetzung von Ergebnissen aus Hochdurchsatz-Screenings.
Hauptmerkmale sind:
- EXS73565 in Kombination mit Zanubrutinib zeigte eine tiefere und dauerhaftere Wirksamkeit in Modellen von B-Zell-Malignomen.
- EXS74539 zeigte plättchenbezogene Effekte in AML-Modellen.
- Identifizierung von 12 potenziellen pharmakodynamischen Biomarkern für die Aktivität von LSD1-Inhibitoren.
- Sowohl EXS73565 als auch EXS74539 werden voraussichtlich Anfang 2025 in klinische Studien starten.
- EXS73565 (MALT1 inhibitor) combined with zanubrutinib showed enhanced efficacy in B-cell malignancy models
- EXS74539 (LSD1 inhibitor) demonstrated platelet level effects in AML models
- Identification of 12 potential pharmacodynamic biomarkers for LSD1 inhibitor activity
- Both EXS73565 and EXS74539 are expected to enter clinical studies in early 2025
- Successful identification and validation of novel essential regulators of a key oncogenic pathway through Xcellomics collaboration
- None.
Insights
The preclinical data presented by Exscientia at ENA 2024 showcases promising advancements in their AI-designed inhibitors for cancer treatment. Key highlights include:
- Combination potential of MALT1 inhibitor EXS73565 with BTK inhibitors for enhanced efficacy in B-cell malignancies
- Efficacy of LSD1 inhibitor EXS74539 in AML models with impact on platelet levels
- Identification of pharmacodynamic biomarkers for LSD1 inhibitor treatment
These findings demonstrate Exscientia's progress in developing potentially best-in-class molecules with improved properties. The company's AI-driven approach appears to be yielding candidates with enhanced selectivity and efficacy profiles. While still in preclinical stages, the data suggests potential for addressing unmet needs in cancer treatment, particularly in B-cell malignancies and AML.
The Xcellomics collaboration also highlights Exscientia's capabilities in rapidly translating high-throughput screening results into drug discovery programs. This could accelerate the company's pipeline development in oncology.
For investors, these advancements indicate Exscientia's growing potential in the competitive oncology drug development space. However, it's important to note that clinical trials are still pending, with EXS73565 and EXS74539 expected to enter the clinic in early 2025.
Demonstrated combination potential for MALT1 and BTK inhibitors in models of B-cell malignancies
Data highlights efficacy of ‘539 in a preclinical AML model, with limited impact on platelet levels
Identified PD biomarkers related to LSD1 inhibitor treatment
“As our precision-designed LSD1 and MALT1 inhibitors continue to progress towards the clinic, we are excited to share new preclinical data from both programmes,” said David Hallett, Ph.D., interim Chief Executive Officer and Chief Scientific Officer of Exscientia. “These posters, as well as an additional focus on our assay development, highlight the potential of our platform to design best-in-class molecules with improved properties. As our state-of-the-art automation facility continues to ramp up in scale, we look forward to further accelerating the design and development of future molecules.”
The ENA posters will be available on the Exscientia website from their time of presentation.
Poster Presentations
Title: Combining next-generation BTK and MALT1 inhibitors to enhance efficacy and therapeutic utility in B-cell malignancies
Session Title: Combination therapies
Catalog Number: 218
Poster Board Number: PB206
Date/Time: Thursday, October 24 / 9:00 a.m. – 5:30 p.m. CEST
- EXS73565 (‘565) is a potent, selective allosteric MALT1 inhibitor designed to have an improved safety profile, with clinical studies expected to start in early 2025
- Combining MALT1 inhibitors, such as ‘565, with BTK inhibitors has the potential to provide enhanced efficacy in B-cell malignancies, by greater inhibition of pathogenic nuclear factor-kappa B (NF-kB) signalling and addressing BTK-resistance mechanisms
- Exscientia researchers combined ‘565 with the BTK inhibitor zanubrutinib and observed deeper, more durable efficacy responses in xenograft models of B-cell malignancies, with long-lasting tumour eradication seen for activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL)
- Studies also confirmed target pathway biology engagement, with ‘565 alone and in combination with zanubrutinib inhibiting NF-kB target gene expression in in vivo models
- Overall, the selective profiles of ‘565 and zanubrutinib may maximise the therapeutic index of MALT1 and BTK inhibition in combination, providing scope for enhanced efficacy for patients with B-cell malignancies
Title: In vivo pharmacokinetics, pharmacodynamics and anti-tumour efficacy of EXS74539: A novel, reversible LSD1 inhibitor for acute myeloid leukaemia
Session Title: Epigenetic modulators (HDAC bromodomain modulators, EZH2)
Catalog Number: 250
Poster Board Number: PB238
Date/Time: Thursday, October 24 / 9:00 a.m. – 5:30 p.m. CEST
- ‘539 is a novel, potent, selective and reversible LSD1 inhibitor, with a highly differentiated profile and designed to be brain penetrant, expected to enter the clinic in early 2025
- The poster highlights that by combining ex vivo perturbation of primary human acute myeloid lymphoma (AML) samples with ‘539 and omics profiling, 12 potential pharmacodynamic (PD) biomarker gene candidates were identified that correlate with LSD1 inhibitor activity
- Upregulation of the identified biomarker gene candidates was confirmed in an in vivo AML xenograft model post ‘539 treatment
- Treatment of the in vivo model with the reversible inhibitor ‘539 resulted in limited platelet level effects, highlighting how ‘539 was designed to maximise target engagement while limiting thrombocytopenia
Title: Xcellomics: Powering rapid translation of HTS outputs to AI-driven drug discovery programmes
Session Title: Functional genomics
Catalog Number: 414
Poster Board Number: PB402
Date/Time: Friday, October 25 / 9:00 a.m. – 3:00 p.m. CEST
-
Xcellomics is a collaboration between Exscientia and The Centre for Medicines Discovery at the University of
Oxford , used to rapidly translate the results of cell-based, high-throughput screens into transformative oncology therapies - The collaboration has successfully identified and validated novel essential regulators of a key oncogenic pathway
- Automated assay development and chemical hit ID performed by Exscientia rapidly pushed these novel therapeutic targets into drug discovery programmes
About Exscientia
Exscientia is a technology-driven drug design and development company, committed to creating more effective medicines for patients, faster. Exscientia combines precision design with integrated experimentation, aiming to invent and develop the best possible drugs in the most efficient manner. Operating at the interfaces of human ingenuity, artificial intelligence (AI), automation and physical engineering, we pioneered the use of AI in drug discovery as the first company to progress AI-designed small molecules into a clinical setting. We have developed an internal pipeline focused on oncology, while our partnered pipeline extends to many other therapeutic areas. By leading this new approach to drug creation, we believe we can change the underlying economics of drug discovery and rapidly advance the best scientific ideas into medicines for patients.
For more information visit us on www.exscientia.com or follow us on LinkedIn @ex-scientia and X @exscientiaAI.
Forward-looking Statements
This press release contains certain forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates,” “believes,” “expects,” “intends,” and “projects” or similar expressions are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding the combination potential for MALT1 and BTK inhibitors in models of B-cell malignancies, PD biomarkers related to LSD1 inhibitor treatment and the benefits of reversible LSD1 inhibition on platelets as well as the ability of Exscientia’s technology to design compounds to create more effective medicines for patients. Such statements are subject to a number of risks, uncertainties and assumptions, including those related to: the initiation, scope and progress of Exscientia’s and its partners’ planned and ongoing preclinical studies and clinical trials and ramifications for the cost thereof; clinical, scientific, regulatory and technical developments; the development and deployment of new technology and facilities; the process of discovering, developing and commercialising product candidates that are safe and effective for use as human therapeutics and the endeavour of building a business around such product candidates; and the process of creating a combined company with Recursion Pharmaceuticals and subsequent activities by any such combined company. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section and other sections of Exscientia’s Annual Report on Form 20-F, filed with the Securities and Exchange Commission (SEC) on March 21, 2024, and other filings that Exscientia makes with the SEC from time to time (which are available at https://www.sec.gov/), the events and circumstances discussed in such forward-looking statements may not occur, and Exscientia’s actual results could differ materially and adversely from those anticipated or implied thereby. Although Exscientia’s forward-looking statements reflect the good faith judgement of its management, these statements are based only on facts and factors currently known by the Company. As a result, investors are cautioned not to rely on these forward-looking statements. Exscientia undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.
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Source: Exscientia plc
FAQ
What are the key findings for Exscientia's MALT1 inhibitor EXS73565 presented at ENA 2024?
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