Editas Medicine Reports New In Vivo Data Highlighting the Potential of Editas’ Gene Upregulation Strategy in HSCs at the American Society of Gene and Cell Therapy Annual Meeting
In non-human primates, a single intravenous dose achieved up to 47% HBG1/2 editing levels in HSCs. In humanized mice, the treatment reached 48% editing in long-term HSCs. Both results exceeded the 25% threshold required for therapeutic benefit.
The company's tLNP formulation showed improved liver de-targeting compared to standard LNPs, and utilizes proprietary AsCas12a technology for high-efficiency editing while minimizing off-target effects. The approach mimics naturally occurring mechanisms of hereditary persistence of fetal hemoglobin (HPFH).
Nei primati non umani, una singola dose endovenosa ha raggiunto fino al 47% di editing HBG1/2 nelle HSC. Nei topi umanizzati, il trattamento ha raggiunto il 48% di editing nelle HSC a lungo termine. Entrambi i risultati superano la soglia del 25% richiesta per un beneficio terapeutico.
La formulazione tLNP dell'azienda ha mostrato un miglior de-targeting epatico rispetto alle LNP standard, utilizzando la tecnologia proprietaria AsCas12a per un editing ad alta efficienza minimizzando gli effetti off-target. L'approccio imita i meccanismi naturali della persistenza ereditaria dell'emoglobina fetale (HPFH).
En primates no humanos, una sola dosis intravenosa logró hasta un 47% de edición HBG1/2 en HSC. En ratones humanizados, el tratamiento alcanzó un 48% de edición en HSC a largo plazo. Ambos resultados superaron el umbral del 25% requerido para beneficio terapéutico.
La formulación tLNP de la compañía mostró una mejor desorientación hepática en comparación con las LNP estándar, y utiliza la tecnología propietaria AsCas12a para una edición de alta eficiencia minimizando los efectos fuera del objetivo. El enfoque imita los mecanismos naturales de persistencia hereditaria de la hemoglobina fetal (HPFH).
비인간 영장류에서 단일 정맥 주사로 HSC 내 최대 47%의 HBG1/2 편집률을 달성했습니다. 인간화 마우스에서는 장기 HSC에서 48% 편집에 도달했습니다. 두 결과 모두 치료적 이점을 위한 25% 기준치를 초과했습니다.
회사의 tLNP 제형은 표준 LNP에 비해 간 비표적화가 개선되었으며, 독자적인 AsCas12a 기술을 활용하여 높은 편집 효율과 최소한의 오프타겟 효과를 구현합니다. 이 접근법은 태아 헤모글로빈의 유전적 지속성(HPFH)의 자연 발생 메커니즘을 모방합니다.
Chez les primates non humains, une dose intraveineuse unique a atteint jusqu'à 47% d'édition HBG1/2 dans les HSC. Chez les souris humanisées, le traitement a atteint 48% d'édition dans les HSC à long terme. Les deux résultats dépassent le seuil de 25% requis pour un bénéfice thérapeutique.
La formulation tLNP de la société a montré une meilleure dé-ciblage hépatique par rapport aux LNP standard, et utilise la technologie propriétaire AsCas12a pour une édition à haute efficacité tout en minimisant les effets hors cible. Cette approche imite les mécanismes naturels de persistance héréditaire de l'hémoglobine fœtale (HPFH).
Bei nicht-menschlichen Primaten erreichte eine einzelne intravenöse Dosis bis zu 47% HBG1/2-Editing in HSC. Bei humanisierten Mäusen erreichte die Behandlung 48% Editing in langzeitigen HSC. Beide Ergebnisse übertrafen die 25% Schwelle, die für einen therapeutischen Nutzen erforderlich ist.
Die tLNP-Formulierung des Unternehmens zeigte eine verbesserte Leber-De-Targeting im Vergleich zu Standard-LNPs und nutzt proprietäre AsCas12a-Technologie für hocheffizientes Editing bei minimalen Off-Target-Effekten. Der Ansatz ahmt die natürlich vorkommenden Mechanismen der erblichen Persistenz von fetalem Hämoglobin (HPFH) nach.
- Achieved 47-48% editing levels in both NHP and humanized mice studies, significantly exceeding the 25% threshold needed for therapeutic benefit
- Demonstrated successful single-dose administration with high efficiency HSC delivery
- Showed improved liver de-targeting compared to standard LNPs, potentially reducing side effects
- Uses clinically validated approach with proprietary AsCas12a technology for high efficiency and minimal off-target editing
- Still in pre-clinical development phase
- Results limited to animal studies, human trials yet to be conducted
Insights
Editas' preclinical data shows promising in vivo gene editing efficiency for sickle cell disease/beta thalassemia, exceeding therapeutic thresholds.
Editas Medicine has shared compelling preclinical data for their in vivo gene editing approach targeting sickle cell disease and beta thalassemia. The results demonstrate 48% editing of HBG1/2 in long-term HSCs in humanized mice and up to 47% editing in non-human primates following a single intravenous dose of their proprietary targeted lipid nanoparticle (tLNP). These editing levels substantially exceed the 25% threshold predicted necessary for therapeutic benefit.
What makes this approach particularly noteworthy is the in vivo delivery mechanism. Current approved gene editing therapies for these hemoglobinopathies require extracting, editing, and reinfusing a patient's cells—an expensive, complex process requiring specialized centers. An in vivo approach could dramatically improve accessibility by potentially eliminating the need for cell collection and complicated ex vivo processing.
The company's strategy mimics naturally occurring mechanisms of hereditary persistence of fetal hemoglobin (HPFH) by targeting HBG1/2 promoters. This approach has already shown clinical validation with their investigational medicine reni-cel, which demonstrated robust increases in fetal hemoglobin and total hemoglobin. The use of their proprietary AsCas12a nuclease also suggests high editing efficiency with minimized off-target effects.
An additional technical advantage appears in their tLNP formulation, which shows significant de-targeting of the liver compared to standard LNPs. This suggests improved tissue selectivity—addressing a key challenge in nucleic acid delivery technology and potentially enhancing the therapeutic index of their treatment.
Data demonstrate therapeutically relevant editing levels using a clinically validated strategy, supporting its development as a novel, in vivo approach to treating sickle cell disease and beta thalassemia
CAMBRIDGE, Mass., May 14, 2025 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (Nasdaq: EDIT), a pioneering gene editing company, today shared new in vivo data demonstrating therapeutically relevant levels of HBG1/2 promoter editing in hematopoietic stem cells (HSCs) with a single dose of proprietary targeted lipid nanoparticle (tLNP) in humanized mice and non-human primates (NHPs). This clinically validated approach targeting HBG1/2 promoters to upregulate fetal hemoglobin (HbF) is in pre-clinical development as a potential transformative in vivo gene editing medicine for the treatment of sickle cell disease and beta thalassemia. The Company reported these data in a presentation available today and will detail the data in an oral presentation today at 1:30 p.m. CT/2:30 p.m. ET at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in New Orleans, LA, and virtually.
In these studies, the Company’s proprietary tLNP formulation delivered HBG1/2 promoter editing cargo to HSPCs and/or HSCs in humanized mice (mice engrafted with human CD34+ cells) and in NHPs. In an ongoing NHP study, administration of a single intravenous dose of Editas Medicine’s proprietary tLNP demonstrated high efficiency HSC delivery and achieved up to
“These findings are very encouraging and further support our approach to developing a potentially first- and best-in-class in vivo gene edited medicine for the treatment of sickle cell disease and beta thalassemia,” said Linda C. Burkly, Ph.D., Executive Vice President and Chief Scientific Officer, Editas Medicine. “We believe that translating these preclinical results to the clinic will address the continuing significant unmet need for a transformative gene edited medicine with the potential to improve the lives of people living with sickle cell disease and beta-thalassemia around the world.”
Editas Medicine’s in vivo HSC program targets HBG1/2 promoters to mimic naturally occurring mechanisms of hereditary persistence of fetal hemoglobin (HPFH) and utilizes proprietary AsCas12a to edit with high efficiency and minimize off-target editing. Editing the HBG1/2 promoters with AsCas12a with the investigational medicine reni-cel led to robust increases in fetal hemoglobin (HbF) and total hemoglobin (Hb) in clinical trials.
Oral Presentation Details:
Title: In Vivo Delivery of HBG1/2 Promoter Editing Cargo to HSC of Humanized Mouse and Non-Human Primate with Lipid Nanoparticles
Session Date and Time: Wednesday, May 14, 2025, 1:30 p.m. – 1:45 p.m. CT
Session Title: Translational Applications of Base and Prime Editors
Room: 265-268
Final Abstract Number: AMA353
Additional Editas Medicine presentations are below. Abstracts can be accessed on the ASGCT website, and the presentations will be posted on the Editas Medicine website during the conference.
Poster Presentations:
Title: Design and Development of Improved LNP Targeting Ligands for In Vivo Hematopoietic Stem Cell Editing
Session Date and Time: Tuesday, May 13, 2025, 6:00 p.m. – 7:30 p.m. CT
Session Title: Tuesday Poster Reception
Presentation Room: Poster Hall, Hall 12
Final Abstract Number: AMA245
Title: Design of Chemically Modified AsCas12a Guide RNAs for Increased Potency of LNP-Delivered Gene Editing Cargos
Session Date and Time: Tuesday, May 13, 2025, 6:00 p.m. – 7:30 p.m. CT
Session Title: Tuesday Poster Reception
Presentation Room: Poster Hall, Hall 12
Final Abstract Number: AMA420
Title: In Vivo Gene Editing and Disease-Associated Biomarker Reduction for Multiple Liver Targets in Non-human Primate Using AsCas12a Nuclease Delivered by LNP
Session Date and Time: Wednesday, May 14, 2025, 5:30 p.m. – 7:00 p.m. CT
Session Title: Wednesday Poster Reception
Presentation Room: Poster Hall, Hall 12
Final Abstract Number: AMA640
Title: In Vivo CRISPR Editing of Genetic Regulatory Regions Results in Functional Upregulation of Target Protein and Meaningful Reduction of Disease-Associated Biomarker in Mice
Session Date and Time: Wednesday, May 14, 2025, 5:30 p.m. – 7:00 p.m. CT
Session Title: Wednesday Poster Reception
Presentation Room: Poster Hall, Hall 12
Final Abstract Number: AMA351
About Editas Medicine
As a pioneering gene editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas12a and CRISPR/Cas9 genome editing systems into a robust pipeline of in vivo medicines for people living with serious diseases around the world. Editas Medicine aims to discover, develop, manufacture, and commercialize transformative, durable, precision in vivo gene editing medicines for a broad class of diseases. Editas Medicine is the exclusive licensee of Broad Institute’s Cas12a patent estate and Broad Institute and Harvard University’s Cas9 patent estates for human medicines. For the latest information and scientific presentations, please visit www.editasmedicine.com.
Media and Investor Contact: ir@editasmed.com
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