CorrectSequence Therapeutics’ (Correctseq’s) base editing drug "CS-101 Injection" targeting transfusion-dependent β-thalassemia has obtained IND approval from the National Medical Products Administration (NMPA) of China on April 2, 2024 (acceptance number: CXSL2400021). This is the Chinese first base editing therapy with β-thalassemia. Correctseq is initiating the Phase 1 clinical study for CS-101 (clincialtrials.gov  reference # NCT06291961).

Public Information of NMPA

Correctseq’s CS-101 is a personalized treatment that begins with the collection of autologous hematopoietic stem cells from β-thalassemia patients. The transformer Base Editor (tBE) technology (Wang et al., Nat Cell Biol, 2021), developed by scientists at ShanghaiTech University, is then used to precisely edit the DNA sequence of the promoter region of the gene encoding γ-globin (HBG1/2) to mimic the naturally occurring single-nucleotide variant in the population with hereditary persistence of fetal hemoglobin, thereby reactivating the γ-globin expression to produce functional HbF. Finally, the edited stem cells are infused back into the patient, enabling the patient to continuously produce blood cells with intact hemoglobin and eliminating the need for frequent blood transfusions. While several gene editing strategies have been explored to restore normal hemoglobin levels in β-thalassemia patients, it has been shown that base editing of the BCL11A binding site at the HBG1/2 promoter by tBE – as in the CS-101 treatment – exhibited the highest level of γ-globin reactivation both in vitro and in vivo (Han et al., Cell Stem Cell, 2023). 

Compared with other CRISPR-based β-thalassemia gene editing therapies, CS-101 using tBE technology shows effective hematopoietic reconstruction, earlier recovery to the normal range of hemoglobin level, and shorter time to achieve transfusion independence. Importantly, CS-101 does not harbor safety risks such as large DNA fragment deletions, chromosomal rearrangements, or off-target mutations, owing to the innovative tBE technology.

Up to now, several patients with transfusion-dependent β-thalassemia treated with the tBE-based gene editing therapy have all achieved transfusion independence. The first patient’s fetal hemoglobin (HbF) level has been continuously stabilized to ~130 g/L, and has sustained transfusion-free for nearly five months. This is the world’s first report of successful clinical cure of hemoglobinopathy with base editing therapy. At the same time, no serious adverse events related to CS-101 injection are reported. This shows that CS-101 injection has good safety and efficacy, bringing hope for “one-time treatment, life-time cure” to patients with severe diseases worldwide. The IND approval of the CS-101 injection will promote the rapid transformation of China's original base editing technology into drugs to benefit more β-thalassemia patients.

Correctseq use innovative base editing technology to help people with severe disease. We are developing multiple pipelines targeting genetic diseases, cancer immunotherapy, metabolic disorders, and cardiovascular diseases, determined to efficiently promote the clinical translation of innovative gene editing technologies, bringing hope of complete cure to more patients around the world.

For more clinic trails information, please contact: CT@correctsequence.com