CS-101 / CorrectSequence Therap - LARVOL DELTA

Rapid, efficient and durable fetal hemoglobin production following CS-101 treatment in transfusion-dependent β-thalassemia participants: An autologous, ex vivo edited CD34+ stem cell product using the innovative transformer base editor (tBE) (ASH 2025) - P1 | " Participants aged 12-35 years with transfusion-dependent β-thalassemia (TDT) with ahistory of ≥ 8 units packed RBC transfusions in the past 12 months prior to the screening wereeligible to participate in 1 of the 2 ongoing CS-101 clinical trials (NCT06024876, NCT06291961).After enrollment, participants undergo collection of autologous hematopoietic stem cells (HSCs),ex vivo base editing, busulfan conditioning to prepare the bone marrow, infusion of CS-101product (the edited HCSs), and subsequent monitoring for safety, efficacy, and clinical outcomes.Key safety endpoints include adverse events, and engraftment. The data demonstrate clinically significant increases in both total Hb and HbF,prompt and durable engraftment, and therapeutic benefits for all the participants who receivedCS-101 infusion. The treatment prompted an early and substantial elevation in HbF level,pancellular distribution, and stable editing efficiency. CS-101 represents the first reported..."

Preclinical • Beta-Thalassemia • Genetic Disorders • Sickle Cell Disease • CD34 • HBB

Development of Best-in-Class Gene Editing Therapy for β-Hemoglobinopathies Using Innovative Transformer Base Editor (tBE) (ASH 2023) - "Pre-clinical in vivo studies showed that while tBE-mediated editing of HSC induces robust γ-globin expression, tBE did not cause adverse effect on the engraftment or differentiation of the HSC in mice after transplantation. Clinical study for CS-101 is underway and it holds great promise to become the best-in-class gene editing treatment for β-hemoglobinopathies."

Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HBB

Rapid, Efficient and Durable Fetal Hemoglobin Production Following CS-101 Treatment in Transfusion-Dependent β-Thalassemia Participants: An Autologous, Ex Vivo Edited CD34+ Stem Cell Product Using the Innovative Transformer Base Editor (tBE) (ASH 2024) - P1 | "After enrollment, participants undergo collection of autologous hematopoietic stem cells (HSCs), ex vivo base editing, busulfan conditioning to prepare the bone marrow, infusion of CS-101 product (the edited HCSs), and subsequent monitoring for safety, efficacy, and clinical outcomes. CS-101 represents the first reported clinical base editing therapy for β-hemoglobinopathies and has the potential to become the best-in-class gene editing therapy for TDT. Submitted on behalf of the CS-101 Investigators."

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

TREATMENT OF PATIENTS WITH SEVERE TRANSFUSION-DEPENDENT ß-THALASSEMIA WITH CS-101, AN AUTOLOGOUS, EX VIVO EDITED, CD34+ HEMATOPOIETIC STEM CELL PRODUCT USING INNOVATIVE TRANSFORMER BASE EDITOR (TBE) (EHA 2025) - P1 | "After enrollment, participants undergo the collection of autologous hematopoietic stem cells (HSCs), ex vivo base editing, busulfan conditioning to prepare the bone marrow niche, infusion of the CS-101 product (the edited HSCs), and subsequent monitoring for safety, efficacy, and clinical outcomes. The data demonstrate clinically significant increases in both total Hb and HbF, prompt and durable engraftment, and therapeutic benefits for all participants who received the CS-101 infusion. The treatment prompted an early and substantial elevation in HbF levels, pancellular distribution, and stable editing efficiency. CS-101 represents the first reported clinical base editing therapy for β-hemoglobinopathies and has demonstrated outstanding therapeutic efficacy and safety."

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

CS-101 TREATMENT IN PEDIATRIC TRANSFUSION-DEPENDENT Β-THALASSEMIA LEADS TO RAPID, SUSTAINED FETAL HEMOGLOBIN PRODUCTION VIA EX VIVO EDITING OF AUTOLOGOUS CD34+ CELLS USING TRANSFORMER BASE EDITOR (EBMT 2025) - P1 | "Following enrollment, participants underwent autologous hematopoietic stem cell (HSC) collection, ex vivo base editing, busulfan conditioning, infusion of CS-101 (edited HSCs), and monitoring for safety, efficacy, and clinical outcomes. The data show that all children aged 14 and younger receiving CS-101 demonstrated significant increases in Hb and HbF, with rapid and sustained engraftment, providing therapeutic benefits. This is the first clinical base-editing therapy for β-hemoglobinopathies, conducted in children, and may become a leading gene-editing treatment for clinical cure of transfusion-dependent thalassemia (TDT) in children. Clinical Trial Registry: NCT06065189 and NCT06291961"

Preclinical • Beta-Thalassemia • Genetic Disorders • Leukopenia • Oncology • Pediatrics • Sickle Cell Disease • Solid Tumor • CD34 • HBB

A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd | Trial primary completion date: Feb 2025 ➔ Jun 2025

Trial primary completion date • Beta-Thalassemia • Genetic Disorders

Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Children's Hospital of Fudan University | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Oct 2024 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

A Follow-up Study to Evaluate the Long-term Safety and Efficacy in Participants Who Received CS-101 Injection (clinicaltrials.gov) - P=N/A | N=8 | Enrolling by invitation | Sponsor: CorrectSequence Therapeutics Co., Ltd

New trial • Beta-Thalassemia • Genetic Disorders • Transplantation

A Long-term Follow-up Study in Participants Who Received CS-101 (clinicaltrials.gov) - P=N/A | N=5 | Enrolling by invitation | Sponsor: CorrectSequence Therapeutics Co., Ltd

New trial • Beta-Thalassemia • Genetic Disorders • Transplantation

CS-101 in Patients With Sickle Cell Disease (clinicaltrials.gov) - P1 | N=5 | Recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd

New P1 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

TREATMENT OF PATIENTS WITH SEVERE TRANSFUSION-DEPENDENT Β-THALASSEMIA WITH CS-101, AN AUTOLOGOUS, EX VIVO EDITED, CD34+ HEMATOPOIETIC STEM CELL PRODUCT USING INNOVATIVE TRANSFORMER BASE EDITOR (TBE) (EHA 2024) - "Peripheral CD34+ HSCs werecollected by apheresis after mobilization with G-CSF and plerixafor...All patients had grade 3 or grade 4 leukopenia, neutropenia, thrombocytopenia, stomatitis, which iscommonly associated with myeloablative busulfan conditioning... Our data demonstrate clinically significant increases in HbF and evidence of benefit for all 3 treated patientsafter CS-101 infusion. Consistent with pre-clinical studies, editing of the BCL11A binding motif in the promoterregion of HBG1/2 by tBE triggers more robust HbF expression than editing of the BCL11A erythroid enhancerby CRISPR/Cas9 nucleases. CS-101 is the world's first reported base editing therapy for β-hemoglobinopathies."

Preclinical • Beta-Thalassemia • Bone Marrow Transplantation • Dental Disorders • Genetic Disorders • Hematological Disorders • Leukopenia • Neutropenia • Sickle Cell Disease • Stomatitis • Thrombocytopenia • Transplantation • CD34 • HBB

CS-101 in Patients With β-thalassemia (clinicaltrials.gov) - P1 | N=10 | Enrolling by invitation | Sponsor: CorrectSequence Therapeutics Co., Ltd | Recruiting ➔ Enrolling by invitation

Enrollment status • Beta-Thalassemia • Genetic Disorders

A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Beta-Thalassemia • Genetic Disorders

CS-101 in Patients With β-thalassemia (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders

A Safety and Efficacy Study Evaluating CS-101 in Subjects With β-Thalassemia Major (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders

Development of Best-in-Class Gene Editing Therapy for β-Hemoglobinopathies Using Innovative Transformer Base Editor (tBE) (ASGCT 2024) - "CS-101 holds great promise to become the best-in-class gene editing therapy and first-in-class base editing therapy for β-hemoglobinopathies. Plain Language Summary: CorrectSequence Therapeutics' first pipeline, CS-101, uses transformer Base Editor (tBE) to precisely edit the binding motif of transcription repressor BCL11A in HBG1/2 promoter in the CD34+HSC to trigger the reactivation of fetal hemoglobin for treatment of β-Hemoglobinopathies. Compared with the commonly used gene editing methods such as CRISPR/Cas nucleases or other base editors, tBE avoids causing DNA double strand breaks or off-target mutations and exhibits more potent globin reactivation."

Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34 • HBB

A Clinical Trial Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd

New P1 trial • Beta-Thalassemia • Genetic Disorders

A Safety and Efficacy Study Evaluating CS-101 in Subjects With β-Thalassemia Major (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd

New P1 trial • Beta-Thalassemia • Genetic Disorders

Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major (clinicaltrials.gov) - P1 | N=5 | Recruiting | Sponsor: Children's Hospital of Fudan University | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major (clinicaltrials.gov) - P1 | N=5 | Not yet recruiting | Sponsor: Children's Hospital of Fudan University

New P1 trial • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia (clinicaltrials.gov) - P1 | N=5 | Recruiting | Sponsor: CorrectSequence Therapeutics Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders