renizgamglogene autogedtemcel (EDIT-301) / Editas Medicine - LARVOL DELTA

Efficacy, Safety, and Treatment-Delivery Feasibility of Autologous Gene Therapy for Sickle Cell Disease: A Systematic Review With Descriptive Synthesis of Clinical Trials. (PubMed, Eur J Haematol) - "Autologous gene therapy for SCD produces substantial short- to medium-term reductions in severe VOEs and improves hemoglobin biology, but certainty remains limited by single-arm designs, small samples, evolving protocols, and incomplete long-term follow-up. Successful delivery depends on separable processes: transfusion preparation, mobilization, apheresis collection, ex vivo manufacturing/editing, product release, conditioning, and reinfusion. Long-term safety, fertility, organ outcomes, reimbursement, and global scalability remain unresolved implementation barriers."

Journal • Review • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat Sickle Cell Disease. (PubMed, N Engl J Med) - P1/2 | "Treatment with reni-cel led to normalization of the total hemoglobin level and an increase in the percentage of fetal hemoglobin, with no vaso-occlusive events occurring in 27 of 28 patients after infusion. These results support further investigation of this gene-editing approach in the treatment of severe sickle cell disease. (Funded by Editas Medicine; RUBY ClinicalTrials.gov number, NCT04853576.)."

Journal • Bone Marrow Transplantation • CNS Disorders • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat β-Thalassemia. (PubMed, N Engl J Med) - P1/2 | "Treatment with reni-cel resulted in rapid neutrophil engraftment, an increase in fetal hemoglobin expression, and transfusion independence. These data support further investigation of Cas12a gene editing of the promoters of HBG1 and HBG2 in the treatment of transfusion-dependent β-thalassemia. (Funded by Editas Medicine; EdiThal ClinicalTrials.gov number, NCT05444894.)."

Journal • Beta-Thalassemia • Genetic Disorders • Infectious Disease • Inflammation • Pneumonia

CRISPR-Cas12a gene editing of the HBG1/2 promoters leads to sustained normalization of total hemoglobin and increased fetal hemoglobin in patients with severe sickle cell disease: Updated Results from the RUBY trial (ASH 2025) - P1/2 | "After plerixafor mobilization, autologous CD34+hematopoietic stem and progenitor cells were collected from each patient by apheresis...The safety profile ofreni-cel was consistent with busulfan. Data from the RUBY trial continue to demonstrate early and sustained normalization oftotal Hb and durable increases in HbF following reni-cel infusion, with 31 of 32 patients VOE-free at thetime of this data cut. These updated findings, derived from a larger patient cohort and extended follow-up period, validate this novel gene-editing approach as a potential one-time treatment for patients withsevere SCD."

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1 • HP

AsCas12a Gene Editing of HBG1/2 Promoters with EDIT-301 Results in Rapid and Sustained Normalization of Hemoglobin and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease and Transfusion-Dependent Beta-Thalassemia (ASH 2023) - P1/2 | "Autologous CD34+ hematopoietic stem and progenitor cells collected by apheresis after plerixafor (RUBY) or plerixafor + filgrastim (EdiThal) mobilization were edited at the HBG1/2 promoters with AsCas12a...The safety profile of EDIT-301 in both SCD and TDT was consistent with myeloablative conditioning with busulfan... These data demonstrated successful engraftment, a rapid and sustained normalization of Hb as early as 4 months after infusion, an increase in HbF and percentage of F-cells, resolution of VOEs (SCD) and transfusion independence (TDT). In addition, there were improvements in key markers of hemolysis (SCD) and a favorable safety profile in EDIT-301-treated patients. EDIT-301 treatment showed promising results for the first clinical use of AsCas12a in both SCD and TDT patients after gene editing of the γ-globin gene (HBG1/2) promoters."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1

Reni-Cel, an Investigational AsCas12a Gene-Edited Cell Medicine, Led to Successful Engraftment, Increased Hemoglobin, and Reduced Transfusion Dependence in Patients with Transfusion-Dependent Beta-Thalassemia Treated in the Edithal Trial (ASH 2024) - P1/2 | "After plerixafor and filgrastim mobilization, autologous CD34+ hematopoietic stem and progenitor cells are collected by apheresis and edited at the HBG1 and HBG2 promoters...The safety profile of reni-cel was consistent with myeloablative conditioning with busulfan...Additionally, patients have been transfusion-independent for up to 14.5 months. These findings, which include additional outcomes, build on clinical evidence to support the continued investigation of reni-cel in the EdiThal clinical trial."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • CD34

Reni-Cel, an Investigational AsCas12a Gene-Edited Cell Medicine, Led to Sustained Hemoglobin Normalization and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease Treated in the RUBY Trial (ASH 2024) - P1/2 | "After plerixafor mobilization, autologous CD34+ hematopoietic stem and progenitor cells are collected by apheresis and edited at the HBG1/2 promoters...The safety profile of reni-cel was consistent with myeloablative conditioning with busulfan...The data also demonstrate an early increase in the percentage of F-cells, improvements in markers of hemolysis, sustained high levels of editing, resolution of VOEs, and a favorable safety profile, with successful engraftment in all patients. These findings, which are based on a larger cohort of patients and additional outcomes, build on clinical evidence that support the continued investigation of reni-cel in the RUBY trial."

Clinical • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HP

Nonclinical evaluation of renizgamglogene autogedtemcel for SCD and TDT. (PubMed, Mol Ther) - "A comprehensive off-target editing evaluation in edited CD34+ cells showed AsCas12a to be highly specific, with no off-target editing detected. In summary, editing CD34+ cells at the HBG1/2 promoter distal BCL11A binding site using AsCas12a phenocopied hereditary persistence of fetal hemoglobin mutations, demonstrating its potential as a gene editing approach for the treatment of β-hemoglobinopathies."

Journal • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34

TARGETED LIPID NANOPARTICLE DELIVERY ENABLES IN VIVO HBG1/2 GENOME EDITING IN NON-HUMAN PRIMATES (EHA 2025) - "This validation is based on the clinical trials of renizgamglogene autogedtemcel (reni-cel), an ex vivo autologous gene editing therapy... Our data demonstrate high efficiency delivery, therapeutically relevant editing levels, and a favorable biodistribution profile, thereby warranting further development of Editas' proprietary HSC-tLNP for editing of the HBG1/2 promoters for the treatment of β-hemoglobinopathies."

Preclinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1 • THY1

In Vivo Delivery of HBG1/2 Promoter Editing Cargo to HSC of Humanized Mouse and Non-Human Primate with Lipid Nanoparticle (ASGCT 2025) - "Ex vivo– based autologous genome editing of the HBG1/2 promoter of hematopoietic stem and progenitor cells (HSPCs) for hematopoietic stem cell transplantation (HSCT) has shown promising results in clinical trials of renizgamglogene autogedtemcel (reni-cel)...Conclusion Our data from humanized mouse and NHP models represent a significant advancement in developing in vivo gene editing therapies for treating β-hemoglobinopathies. As ~30% donor chimerism can significantly ameliorate disease symptoms in patients with SCD, the editing level and percentage of HbF-positive cells achieved with in vivo editing of HBG1/2 promoters may be therapeutically relevant and supports further Disease Focus of Abstract:Sickle Cell"

IO biomarker • Lipid Nanoparticle • Preclinical • Anemia • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • B2M • CD34 • CD38 • HBG1 • THY1

Impact of Different Definitions of Vaso-Occlusion on Efficacy Assessments in Sickle Cell Disease Clinical Trials. (PubMed, Adv Ther) - "Differences exist in definitions of vaso-occlusion and pain events used in SCD clinical trials. Severe VOCs (exa-cel), VOC (voxelotor), and SCPCs (crizanlizumab and L-glutamine) were more broadly inclusive than severe VOEs (lovo-cel and reni-cel) or painful crisis (hydroxyurea). Clinically, these differences resulted in differing numbers of patients being considered free from vaso-occlusion pain events, underscoring the challenge in comparing frequencies of pain events across SCD clinical trials."

Journal • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

EdiThal: EDIT-301 for Autologous Hematopoietic Stem Cell Transplant (HSCT) in Participants With Transfusion-Dependent Beta Thalassemia (TDT) (clinicaltrials.gov) - P1/2 | N=9 | Active, not recruiting | Sponsor: Editas Medicine, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Transplantation

Reni-Cel, an Investigational AsCas12a Gene-Edited Cell Medicine, Led to Sustained Hemoglobin Normalization and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease Treated in the RUBY Trial (TCT-ASTCT-CIBMTR 2025) - P1/2 | "Autologous CD34 + hematopoietic stem and progenitor cells are mobilized using plerixafor, collected, and edited at the HBG1/ 2 promoters. Results with reni-cel treatment were promising, including reliable and prompt engraftment, early Hb normalization, and durable increases in HbF. The data also demonstrate improvement in hemolysis markers, sustained high levels of editing, resolution of VOEs, and a safety profile consistent with myeloablative conditioning with busulfan. These findings build on clinical evidence supporting continued investigation of reni-cel in the RUBY trial."

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1

Reni-Cel, an Investigational AsCas12a Gene-Edited Cell Medicine, Led to Successful Engraftment, Increased Hemoglobin, and Reduced Transfusion Dependence in Patients with Transfusion-Dependent Beta-Thalassemia Treated in the Edithal Trial (TCT-ASTCT-CIBMTR 2025) - P1/2 | "Autologous CD34 + hematopoietic stem and progenitor cells are mobilized using plerixafor and filgrastim, collected, and edited at the HBG1/2 promoters. Results with reni-cel treatment were promising, including successful engraftment, a rapid and sustained increase in total Hb well above the transfusion threshold, increased HbF with pancellular distribution, sustained high levels of editing, and a safety profile consistent with myeloablative conditioning with busulfan. Moreover, pts have been transfusion independent for up to 14.5 mos. These findings build on clinical evidence supporting continued investigation of reni-cel in the EdiThal trial."

Clinical • Beta-Thalassemia • Genetic Disorders • CD34 • HBG1

Editas Medicine Announces Strategic Transition to in vivo Gene Editing Company with Intent to Achieve Human Proof of Concept in Approximately Two Years (GlobeNewswire) - "The Company transition follows the recent in vivo pre-clinical proof of concept in multiple tissues: Hematopoietic Stem Cells (HSCs): Editas achieved ~40% editing of the HBG1/2 promoter site after using a novel, Editas-proprietary targeted lipid nanoparticle (tLNP) for extrahepatic tissue delivery to deliver a single dose of its clinically validated Cas12a editing machinery directly to human hematopoietic stem cells (HSCs) in mice engrafted with human HSCs...The Company intends to share pre-clinical data and further development timelines from these programs in the first quarter of 2025."

Preclinical • Beta-Thalassemia • Hematological Disorders

Editas Medicine Announces...Achievement of In Vivo Preclinical Proof of Concept and Strategic Update (GlobeNewswire) - "The Company is also providing business development and financial updates, including that it initiated a process to partner or out-license reni-cel...In Vivo Proof of Concept Data Highlights: Achieved highly competitive level of in vivo hematopoietic stem and progenitor cell (HSPC) editing utilizing a novel, Editas-proprietary targeted lipid nanoparticle (t-LNP) for extrahepatic tissue delivery in a humanized mouse model, mice engrafted with human hematopoietic stem cells...Further demonstrated that editing with the Company’s proprietary tLNP formulation resulted in the functional outcome of HbF induction, indicated by the presence of HbF expressing human red blood cells (on average 20%) that populate in the host by one month....The Company has engaged Moelis & Company LLC, a leading global independent investment bank, to lead the global process to partner or out-license reni-cel."

Licensing / partnership • Preclinical • Beta-Thalassemia • Hematological Disorders • Sickle Cell Disease

Editas Medicine Announces Progress Towards 2024 Goals... (GlobeNewswire) - "On-track to present a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY trial at the American Society of Hematology (ASH) Annual Meeting and Exposition, December 7-10, 2024; As previously disclosed, the Company has completed enrollment of the adolescent and adult cohorts of the Phase 1/2/3 RUBY trial for SCD. Manufacturing drug product for the initial adolescent cohort patients; The Company continues to dose adult patients in the RUBY trial and has dosed 28 patients to date....On-track to present additional clinical data from the EdiTHAL trial by year-end 2024; The Company completed enrollment of the adult cohort of the EdiTHAL trial for TDT and continues to dose patients."

Clinical data • Trial status • Beta-Thalassemia • Hematological Disorders • Sickle Cell Disease

A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY) (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Editas Medicine, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

EDIT-301-LTFU-001: A Long-Term Follow-Up Study of Participants With Sickle Cell Disease or Transfusion Dependent β-Thalassemia Who Received EDIT-301 (clinicaltrials.gov) - P=N/A | N=54 | Enrolling by invitation | Sponsor: Editas Medicine, Inc. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

RENI-CEL, THE FIRST ASCAS12A GENE-EDITED CELL THERAPY, SHOWS PROMISING PRELIMINARY RESULTS IN KEY CLINICAL OUTCOMES IN TRANSFUSION-DEPENDENT BETA-THALASSEMIA PATIENTS TREATED IN THE EDITHAL TRIAL (EHA 2024) - P1/2 | "Autologous CD34+hematopoietic stem and progenitor cells are collected by apheresis after plerixafor + filgrastim mobilizationand edited at the HBG1/2 promoters with the highly efficient and specific, proprietary gene editing nuclease,AsCas12a. After myeloablative conditioning with busulfan, patients received a single infusion of reni-cel (aminimum of 3 × 106 CD34+ cells/kg) and were monitored for engraftment, total Hb, HbF production,percentage of F-cells, transfusion requirement, and adverse events (AEs) for 24 months... These data demonstrate successful engraftment, an increase in Hb and HbF levels with pancellular distribution,and a favorable safety profile of reni-cel in patients with TDT. Additionally, all patients have been transfusionfree for up to 9. 9 months."

Clinical • Clinical data • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • CD34 • HBG1

RENI-CEL, THE FIRST ASCAS12A GENE-EDITED CELL THERAPY, LED TO HEMOGLOBIN NORMALIZATION AND INCREASED FETAL HEMOGLOBIN IN SEVERE SICKLE CELL DISEASE PATIENTS IN AN INTERIM ANALYSIS OF THE RUBY TRIAL (EHA 2024) - P1/2 | "Autologous CD34+ hematopoietic stem andprogenitor cells are collected by apheresis after plerixafor mobilization and edited at the HBG1/2 promoterswith the highly efficient and specific, proprietary gene editing nuclease, AsCas12a. After myeloablativeconditioning with busulfan, patients received a single infusion of reni-cel (≥3 × 106 CD34+ cells/kg), and weremonitored for engraftment, total hemoglobin (Hb), HbF production, mean HbF concentration/F-cell (MCH-F/F-cell), percentage of F-cells, markers of hemolysis, transfusion requirement, VOEs, and adverse events (AEs) for24 months... These data demonstrate successful engraftment, a rapid and sustained normalization of Hb, an early increasein HbF and percentage of F-cells, improvements in key markers of hemolysis, and a favorable safety profile. Additionally, all patients are VOE-free post-reni-cel infusion as of the cutoff date. Reni-cel treatment showedpromising results for gene editing of the HBG1/2..."

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1

A Long-Term Follow-Up Study of Participants With Sickle Cell Disease or Transfusion Dependent β-Thalassemia Who Received EDIT-301 (clinicaltrials.gov) - P=N/A | N=54 | Not yet recruiting | Sponsor: Editas Medicine, Inc.

New trial • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

AsCas12a Gene Editing of HBG1/2 Promoters with Edit-301 Results in Early and Sustained Normalization of Hemoglobin and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease and Transfusion-Dependent Beta-Thalassemia (TCT-ASTCT-CIBMTR 2024) - P1/2 | "After pharmacokinetically adjusted myeloablative busulfan conditioning, pts received a single infusion of EDIT-301 (≥3 × 106 CD34+ cells/kg) and are monitored for 24 months (mos). These data demonstrate successful engraftment, sustained normalization of Hb as early as Mo 4 after infusion, an increase in HbF and % F-cells, resolution of VOEs (SCD) and transfusion independence (TDT), improvements in key hemolysis markers (SCD) and a favorable safety profile. These promising results for the first clinical use of AsCas12a in SCD and TDT support further investigation of EDIT-301. Updated data with additional outcomes will be presented."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1

EDIT-301 SHOWS PROMISING PRELIMINARY SAFETY AND EFFICACY RESULTS IN THE PHASE I/II CLINICAL TRIAL (RUBY) OF PATIENTS WITH SEVERE SICKLE CELL DISEASE USING HIGHLY SPECIFIC AND EFFICIENT ASCAS12A ENZYME (EHA 2023) - P1/2 | "Autologous CD34 + hematopoietic stem and progenitor cells are collected by apheresis after plerixafor mobilization and edited at the HBG1/HBG2 promoter with AsCas12a...The safety profile of EDIT-301 was consistent with myeloablative conditioning with busulfan, with no reported EDIT-301-related AEs and no serious adverse events (SAEs) after EDIT-301 infusion... These preliminary data demonstrate successful engraftment, a rapid and sustained increase in total Hb, HbF level, and percentage of F-cells, improvements in key markers of hemolysis, and a favorable safety profile in subjects treated with EDIT-301. These preliminary data demonstrated clinical proof of concept and are promising for the first clinical use of AsCas12a-based gene editing of the globin gene ( HBG1/HBG2 ) promoters, thereby supporting further investigation of EDIT-301 in the RUBY clinical trial. Updated data will be presented."

Clinical • P1/2 data • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • HBG1

"Great presentation by Rabi Hanna reporting the initial results of EDIT-301 at #EHA2023 #Frankfurt" (,@hfrangoul)