2025年3月19日，上海——专注于新型基因编辑技术的创新生物医药科技企业正序生物(上海)今日宣布，其自主研发的碱基编辑药物CS-101在治疗β-地中海贫血症(β-地贫)方面再创佳绩，在与广西医科大学第一附属医院合作开展的关于碱基编辑药物CS-101的临床研究中成功治疗了第二位外籍患者——一名来自马来西亚的β-地中海贫血症患者。这是继首例基因编辑治愈来自老挝的β-地贫外籍患者后，正序生物在全球范围内取得的又一重要成果。

▲马来西亚β-地贫患者接受碱基编辑药物(正序生物CS-101)

治疗后已经摆脱输血依赖并回归正常生活

马来西亚地贫患者成功治疗，疗效显著

此次接受正序生物CS-101治疗的马来西亚患者为输血依赖型β-地中海贫血症患者。在接受CS-101治疗前，输血频率达到每月约6单位红细胞。经过CS-101治疗后3个月，患者的总血红蛋白浓度升高至赖120 g/L并且保持稳定，成功实现脱离输血依的目标，回归正常生活。这一成果再次验证了正序生物CS-101在治疗β-地中海贫血症中的卓越疗效和安全性。

首例外籍患者脱离输血依赖已超8个月

正序生物治愈的首例外籍患者——来自老挝的18岁β-地贫女孩，自接受CS-101治疗后，目前已成功脱离输血依赖超过8个月，生活质量显著提升。这一长期疗效表明正序生物CS-101对多种地域性突变导致的地贫患者都具有“一次治疗，终身治愈”的潜力。

正序生物CS-101：Best-in-Class基因编辑疗法

正序生物CS-101注射液采用了公司自主知识产权的高精准变形式碱基编辑器tBE(transformer Base Editor)(Wang et al., Nat Cell Biol, 2021)，该技术由上海科技大学自主研发，具有高效、安全的特点。CS-101通过采集患者自体造血干细胞，利用tBE精准编辑患者自体造血干细胞中的HBG1/2启动子区域，重新激活γ-珠蛋白的表达，重建血红蛋白的携氧功能(Han et al., Cell Stem Cell, 2023)。随后，将编辑后的造血干细胞回输至患者体内，使得患者自身血红蛋白浓度达到健康人水平，从而彻底摆脱输血依赖。

与传统的输血疗法和异体造血干细胞移植相比，CS-101具有显著优势：

基于自体干细胞的基因编辑治疗：无需长时间等待配型，制备周期仅需数周。

高效安全：自主研发的tBE技术避免了DNA双链断裂，有效避免了DNA大片段缺失、染色体异位、脱靶突变等风险。

快速见效：使患者在短时间内完成造血重建，迅速达到健康人血红蛋白水平。

治愈血红蛋白病，造福全球患者和家庭

作为血红蛋白病的一种，β-地中海贫血症是全球最常见的单基因遗传病之一，尤其在东南亚、地中海沿岸国家、中东地区和我国南方地区发病率较高。据统计，东南亚地区约有3亿人携带地中海贫血症突变基因;另一种遗传性血红蛋白病为镰刀型细胞贫血病，在全球多个国家也广泛存在，全球镰刀型细胞贫血病突变基因携带者约占总人口的3.5%，每年大约有30万名婴儿出生时即患有镰刀型细胞贫血病。正序生物CS-101在临床试验上的成功为全球β-地贫等血红蛋白病患者带来了新的希望。

目前，正序生物CS-101注射液针对β-地中海贫血症的临床I期试验已经完成全部患者回输，所有患者均在回输后1个月内摆脱输血依赖，并迅速达到正常人血红蛋白水平，展现了全球同类最好(Best-in-Class)药物的潜力。同时，公司正在全球范围内开展针对镰刀型细胞贫血病的IIT研究。正序生物致力于推进中国原创基因编辑技术的临床转化，开发全球首创(First-in-Class)的碱基编辑治疗药物和同类最好的基因编辑治疗药物，为全球患者带来彻底治愈疾病的曙光。

(特别感谢广西医科大学第一附属医院、上海科技大学及上海临床研究中心)

English Version

CorrectSequence Therapeutics’ CS-101 Successfully Treats Malaysian β-Thalassemia Patient

Shanghai, China, March 19, 2025 — CorrectSequence Therapeutics Co., Ltd. (Correctseq) announced its self-developed base editing therapy, CS-101, has achieved another major milestone in the treatment of β-thalassemia. In collaboration with the First Affiliated Hospital of Guangxi Medical University, CS-101 has successfully treated the second overseas patient — a Malaysian individual with transfusion-dependent β-thalassemia. This milestone follows the first cure of a β-thalassemia overseas patient from Laos, marking another significant global achievement for the company.

A Malaysian β-thalassemia patient who received base editing therapy (Correctseq’s CS-101) in China has been transfusion-free and returned to normal life.

A “Single Treatment, Lifetime Cure” for β-Thalassemia

The Malaysian patient diagnosed with transfusion-dependent β-thalassemia required the transfusion of approximately six units of red blood cells (RBC) per month prior to receiving CS-101 treatment. Following the therapy, the patient’s hemoglobin level reached 120 g/L within three months and has maintained this level as of the report date. The patient successfully achieved independence from blood transfusions. This further validates CS-101’s efficacy and safety.

Meanwhile, the first overseas patient, an 18-year-old girl from Laos, has maintained transfusion independence for over eight months since receiving CS-101 treatment. This long-term efficacy demonstrates that CS-101 has the potential to provide a “single treatment, lifetime cure” for β-thalassemia patients of diverse ethnic backgrounds.

CS-101: A Best-in-Class Gene-Editing Therapy

The underlying principle of CS-101 involves the collection of the patient's own hematopoietic stem cells, followed by the treatment of the transformer Base Editor (tBE). Pioneered by scientists at ShanghaiTech University (Wang et al., Nat Cell Biol, 2021), this technology enables the precise editing of the DNA sequence within the promoter region of the gene responsible for encoding γ-globin (HBG1/2).

By generating a naturally occurring beneficial single-nucleotide variant found in individuals with hereditary persistence of fetal hemoglobin, the tBE reactivates γ-globin expression, resulting in the production of functional HbF (Han et al., Cell Stem Cell, 2023). The edited stem cells are then reintroduced into the patient's body, enabling continuous production of blood cells with functional hemoglobin.

Compared to traditional blood transfusion therapy and allogeneic hematopoietic stem cell transplantation, CS-101 offers several compelling advantages. One of the key benefits is its short preparation period. Another is the elimination of the long waiting time for a matching donor, as it utilizes the patient’s own hematopoietic stem cells. CS-101 has the potential to achieve a "single treatment, lifetime cure" in just a few weeks.

In comparison to other CRISPR-based β-thalassemia gene editing therapies, CS-101 does not cause safety risks associated with large DNA fragment deletions, chromosomal translocation, or off-target mutations. This enhances the overall safety profile of the treatment and reduces potential complications.

Overall, CS-101 offers a promising approach for the treatment of transfusion-dependent β-thalassemia, providing faster and safer hematopoietic reconstruction, quicker restoration of hemoglobin levels, and a shorter path to achieving transfusion independence compared to other therapies.

Curing Hemoglobinopathies to Benefit Global Patients and Families

β-thalassemia, one of the most common single-gene diseases in the world, is particularly prevalent in Southeast Asia, Mediterranean countries, the Middle East, and southern regions of China. It is estimated that approximately 300 million people in Southeast Asia carry the thalassemia mutant gene. Additionally, sickle cell disease, another hereditary hemoglobinopathy, is also widespread in many countries around the world, with about 3.5% of the world’s population carrying the mutation and roughly 300,000 infants born with the disease every year. The success of CS-101 brings new hope to patients with β- thalassemia and other hemoglobinopathies around the world.

To date, the Phase I clinical trial of CS-101 for β-thalassemia has completed the autologous stem cell infusion for all patients, with every patient achieving transfusion independence within one month post-infusion and rapidly reaching normal hemoglobin levels. This demonstrates the potential of CS-101 as the world’s “First-in-Class” base editing therapy and “Best-in-Class” gene editing therapy for β-hemoglobinopathies. In the meantime, an IIT study on sickle cell disease is ongoing. We are recruiting sickle cell patients worldwide. Correctseq is committed to advancing the clinical translation of pioneering gene editing technology, and bringing the hope of a complete cure for patients around the world.

Acknowledgement: The First Affiliated Hospital of Guangxi Medical University, ShanghaiTech University, Shanghai Clinical Research and Trial Center.

About CorrectSequence Therapeutics

CorrectSequence TherapeuticsTM (CorrectseqTM), is a clinical-stage biotech company employing its proprietary transformer Base Editor (tBE) to pioneer next-generation gene editing therapies. Our leading pipeline candidate, CS-101, which utilizes an innovative base editor targeting HBG to cure β-hemoglobinopathies, has obtained IND approval from the China NMPA. Clinical data demonstrates its superior performance. Proof-of-concept (POC) data in mice for in vivo pipelines using tBE-editing therapies via lipid nanoparticle (LNP) delivery are available, including targets for metabolic dysfunction and associated diseases. Ex vivo multiplex editing of T cells on multiple targets simultaneously preserved T cell growth and function in vivo compared to non-edited cells, establishing tBE as the ideal gene editing tool for the next-generation cell therapy development. We are developing multiple pipelines targeting genetic diseases, metabolic disorders, and cardiovascular diseases.

关于正序生物

正序生物(CorrectSequence TherapeuticsTM)是一家专注于新型基因编辑技术、处于临床阶段的生物医药科技公司，致力于利用自主原创的碱基编辑体系，开发突破性精准疗法，造福全球患者和家庭。

公司基于以变形式碱基编辑器tBE为代表的自主知识产权碱基编辑系统搭建了融合多治疗领域的新药发现平台，可长期开发和筛选针对多种遗传性疾病或罕见病的有效治疗靶点。所创建的多种精准疗法，在动物体内实现了疾病治疗靶点上的高效的编辑效率和未检出脱靶的安全性。目前，公司针对遗传疾病、代谢疾病、心血管疾病等布局了多条管线，首条管线CS-101正处于IND临床试验阶段，多位国内外β-地中海贫血症患者在接受治疗后已经摆脱输血依赖。

正序生物孵化自上海科技大学，拥有世界一流的创新技术平台和管线研发能力。在中国科学院上海高等研究院拥有先进的研发和CMC开发中心，在北京华贸中心设立有临床注册和运营中心。目前，公司汇聚了数十位来自全球基因治疗技术开发、药物研发、工艺开发与生产、临床开发和质量与合规等领域的优秀生物医药专家，管理团队和科研团队拥有平均十年以上工业界经验，硕士及以上学位比例超过65%，核心技术人员毕业于国内外顶尖名校。