CorrectSequence Therapeutics Achieves Consistent Clinical Remission Across SCD and TDT Patients

CorrectSequence Therapeutics has achieved a significant milestone with the publication of clinical research in Cell Stem Cell, demonstrating the safety and efficacy of its transformer Base Editor (tBE) for treating sickle cell disease (SCD) and beta-thalassemia (TDT) across different genetic backgrounds. The study, which builds on previous successful trials in China, confirms that tBE-mediated base editing therapy can provide consistent clinical remission and transfusion independence for patients with these blood disorders.

The new research, titled "Clinical base editing for β-hemoglobinopathies across different genetic backgrounds," involved four patients from Nigeria, Laos, Malaysia, and Pakistan. All patients, including a 21-year-old SCD patient from Nigeria, achieved rapid hematopoietic reconstitution and sustained high levels of fetal hemoglobin (HbF) expression, leading to complete transfusion independence or freedom from vaso-occlusive crises (VOCs). The study included three TDT patients from Laos, Malaysia, and Pakistan, who also demonstrated rapid engraftment and sustained hemoglobin levels, achieving sustained transfusion independence.

These results follow the company’s earlier success in treating five Chinese transfusion-dependent TDT patients, who all achieved transfusion independence. The latest findings indicate that the tBE technology is not only effective but also safe and applicable across various ethnicities and genetic mutations, validating the strategy’s universal applicability.

The base-editing therapy, developed with the ultra-high-precision tBE, specifically targets the HBG1/2 promoter region in autologous hematopoietic stem and progenitor cells (HSPCs), reactivating gamma-globin expression. This approach avoids the need for DNA double-strand breaks, which are common in nuclease-based gene editing therapies. Instead, tBE performs precise base conversions, minimizing off-target effects and potential adverse events.

Professor Chen Jia, founder of CorrectSequence Therapeutics and Director of the Gene Editing Center at ShanghaiTech University, stated, "This study confirms the broad applicability of tBE across diverse genetic backgrounds, completing the translational journey from the laboratory to global clinical application. Our team is now expanding this technology to other therapeutic areas, including metabolic and cardiovascular diseases."

Dr. Mou Xiaodun, CEO of CorrectSequence Therapeutics, added, "The data demonstrate tBE as a global Best-in-Class platform, and we are accelerating our pipelines toward global IND submissions to bring China-originated gene editing to more patients worldwide. We are currently exploring the application of tBE in treating hypertriglyceridemia, familial chylomicronemia syndrome, ASCVD, hyperlipoproteinemia, homozygous familial hypercholesterolemia, and metabolic dysfunction-associated steatohepatitis."

To date, CorrectSequence Therapeutics has treated over 30 patients across China, Africa, Southeast Asia, and South Asia, with all patients achieving either transfusion independence or freedom from VOCs, accompanied by sustained, high-level hemoglobin expression. The company’s CS-101, the world’s first ongoing base-editing therapy candidate to enter clinical development, has completed Phase I trials and is now being evaluated in pivotal trials. The longest duration of transfusion independence in Phase I patients approached nearly three years.

These results mark a significant step forward in the treatment of blood disorders, offering hope to millions of patients worldwide. The company’s commitment to advancing gene editing technologies for diverse genetic backgrounds underscores its potential to transform the lives of patients suffering from genetic diseases.