当地时间2025年8月26日，专注于新型基因编辑技术、处于临床阶段的创新生物医药科技企业正序生物(上海)宣布，与广西医科大学第一附属医院合作开展的针对镰刀型细胞贫血病(SCD)的碱基编辑药物CS-101注射液的研究者发起的临床研究(IIT，Investigator Initiated Trial)成功治愈首位患者，患者在治疗后胎儿血红蛋白(HbF)水平显著且持续上升，镰状血红蛋白(HbS)水平显著且持续降低，治疗后6个月起HbF与HbS比例稳定在6.5:3.5，总血红蛋白浓度稳定至120 g/L以上，治疗后6个月中没有出现血管闭塞危象(VOCs，vaso-occlusive crises)，已回归到正常生活中。这是中国首次通过碱基编辑疗法治愈镰刀型细胞贫血病的成功案例。

中国首例接受碱基编辑治疗(正序生物CS-101注射液)的镰刀型细胞贫血病患者在治疗后6个月中没有出现血管闭塞危象并已回归常生活

血红蛋白病是全世界最普遍的单基因遗传病，常见的主要有β-地中海贫血(β-地贫)和镰刀型细胞贫血病。全世界约有7%的人口携带异常血红蛋白基因，每年大约有40万名婴儿出生时患有血红蛋白病。其中，镰刀型细胞贫血病是由于β-珠蛋白基因突变使红细胞呈镰刀状的遗传性疾病，临床表现为慢性溶血性贫血、再发性疼痛危象、易感染、慢性局部缺血导致器官组织损害等，严重时可危及生命。全球约有3.5%的人口携带镰刀型细胞贫血病突变基因，每年约有30万婴儿出生时患有此病，在非洲、地中海沿岸、中东和东南亚等地区发病率较高。

目前，治疗镰刀型细胞贫血病的常规疗法为药物治疗和输血治疗，这两种对症治疗的方式只能缓解疾病带来的痛苦，不能实现彻底治愈。另外还有一种治愈性治疗策略为造血干细胞移植，传统的异体造血干细胞移植需要等待匹配的供体，在实际情况中常常难以实现;基因编辑疗法可以通过基因编辑技术编辑患者的自体造血干细胞激活HbF表达，患者无需等待，治疗周期短，为疾病的彻底治愈带来曙光。

正序生物CS-101注射液是利用上海科技大学自主研发的高精准变形式碱基编辑器tBE(transformer Base Editor)(Wang et al., Nat Cell Biol, 2021)开发的一款针对β-血红蛋白病的基因编辑药物，具有高效、安全的治疗效果。CS-101注射液通过采集患者自体造血干细胞，利用tBE对患者自体造血干细胞中的HBG1/2启动子区域进行精准碱基编辑，模拟健康人群中天然存在的有益碱基突变，重新激活γ-珠蛋白的表达，再将编辑后的造血干细胞回输至患者体内，使得患者胎儿血红蛋白浓度快速升高，有效抑制红细胞镰变，显著减少血管闭塞危象和溶血。

正序生物CS-101注射液治疗的首位镰贫患者是一名来自尼日利亚的21岁女性，在接受CS-101治疗前总血红蛋白浓度为67.3 g/L，有反复发作的血管闭塞危象。患者在2025年2月接受tBE编辑自体干细胞移植治疗后，便快速高效地实现了造血重建，治疗后第13天获得中性粒细胞植入，第21天血小板浓度达到50x10^9/L以上。治疗后1个月胎儿血红蛋白比例从治疗前的基线水平4.4%迅速上升至34.6%，治疗后3个月胎儿血红蛋白比例持续大于60%，镰状血红蛋白比例持续小于40%。治疗后6个月中，没有出现VOCs，且未发现产品相关的不良事件。

正序生物CS-101注射液由于其编辑靶点的高效性和tBE技术的安全性，相较于其他基于CRISPR技术的β-血红蛋白病的编辑疗法，CS-101可以使患者迅速地完成造血重建，更快速并大幅提升胎儿血红蛋白水平从而降低镰刀状血红蛋白的占比，更高效且稳定地阻止红细胞发生镰变;同时不会引发患者基因组DNA大片段缺失、染色体突变、脱靶突变等风险，显示出了更好的有效性和安全性。CS-101注射液已经在临床试验中成功治愈了近20例β-地贫患者和镰刀型细胞贫血病患者，首位β-地贫患者在接受CS-101治疗后已经摆脱输血依赖超过22个月。CS-101注射液有望成为β-血红蛋白病全球首创(First-in-Class)的碱基编辑治疗药物和同类最好(Best-in-Class)的基因编辑治疗药物。

目前，正序生物CS-101注射液针对β-地贫的Ⅰ期临床试验已经完成，所有患者在治疗后均成功摆脱输血依赖，关键性临床试验(Ⅱ/Ⅲ期临床试验)即将开始。针对镰贫的IIT试验和针对β-地贫的关键性临床试验的全球招募正在同步进行。正序生物将快速推进中国自主原创的基因编辑药物CS-101注射液早日上市，为全球罹患严重疾病的患者带来疗效更好、费用更优的选择。

(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

High-Precision Base Editing Clinical Treatment for Sickle Cell Disease

CorrectSequence Therapeutics’ CS-101 Achieves Clinical Cure

Shanghai, August 26, 2025 — CorrectSequence Therapeutics Co., Ltd. (Correctseq), a clinical-stage biotechnology company pioneering transformer Base Editing (tBE) technology for the treatment of severe diseases, today announced the successful treatment of the first sickle cell disease (SCD) patient using its high-precision base-editing therapy CS-101.

The breakthrough was achieved in an Investigator-Initiated Trial (IIT) conducted in collaboration with the First Affiliated Hospital of Guangxi Medical University. The patient demonstrated a significant and sustained increase in fetal hemoglobin (HbF) levels, accompanied by a marked reduction in sickle hemoglobin (HbS). Six months post-treatment, the HbF-to-HbS ratio stabilized at 6.5:3.5, with total hemoglobin consistently exceeding 120 g/L. Over the six-month follow-up period, the patient experienced no vaso-occlusive crises (VOCs) and successfully resumed normal daily activities — marking the first reported clinical cure of sickle cell disease in China using base editing technology.

The patient, a 21-year-old woman from Nigeria, had previously suffered from recurrent VOCs. For six months after receiving CS-101, she remains crisis-free and in good health.

Sickle Cell Disease and the Need for Curative Therapies

Hemoglobinopathies — including SCD and β-thalassemia (β-thal) — are the world’s most common group of monogenic diseases, with approximately 7% of the global population carrying a pathogenic variant. Each year, around 400,000 newborns are affected. SCD, caused by mutations in the β-globin gene, leads to abnormal, sickle-shaped red blood cells, resulting in chronic anemia, recurrent pain crises, increased infection risk, and progressive organ damage. Globally, about 3.5% of the population carries the sickle mutation, with roughly 300,000 affected infants born annually, especially in Africa, the Mediterranean, the Middle East, and South Asia.

Existing treatments such as symptomatic drugs and blood transfusions can alleviate symptoms but do not offer a cure. Hematopoietic stem cell transplantation (HSCT) can be curative, but the requirement for a matched donor limits accessibility. Gene-editing approaches, particularly base editing, can activate fetal hemoglobin in a patient’s own blood cells — eliminating the need for a donor and offering a shorter, potentially safer treatment path.

CS-101: Precision Base Editing for Hemoglobinopathies

CS-101 is a gene-editing therapy based on the high-precision transformer Base Editor (tBE) platform (Wang et al., Nat Cell Biol, 2021), developed by Correctseq’s scientific co-founders. The therapy targets β-hemoglobinopathies by precisely modifying a regulatory element in the promoter of the γ-globin genes (HBG1/2), mimicking naturally occurring single-nucleotide variants found in individuals with hereditary persistence of fetal hemoglobin. This reactivates γ-globin expression to produce functional HbF, which prevents sickling and reduces hemolysis.

In the IIT, the patient began with a baseline hemoglobin level of 67.3 g/L. Following CS-101 treatment in February 2025, she achieved rapid hematopoietic recovery, with neutrophil engraftment in 13 days and platelet counts surpassing 50×10⁹/L in 21 days. Her HbF levels rose from 4.4% to 34.6% within one month, and since the third month post-treatment, HbF levels have remained above 60% while HbS has stayed below 40%. No VOCs or treatment-related adverse events have been reported.

A Safer, More Effective Approach

Compared with conventional CRISPR/Cas9-based therapies, CS-101 delivers efficient hematopoietic recovery and higher HbF-to-HbS ratio, without the risks of large DNA deletions, chromosomal rearrangements, or off-target mutations.

To date, CS-101 has been used to treat nearly 20 patients with β-thalassemia or SCD in clinical trials. The first β-thalassemia patient treated has remained transfusion-free for over 22 months. This positions CS-101 as a potential best-in-class gene-editing therapy — and the world’s first base editing treatment — for β-hemoglobinopathies.

Global Development and Next Steps

The Phase I trial of CS-101 for β-thalassemia has been completed, with all patients achieving transfusion independence. Pivotal Phase II/III trials are set to begin soon, and global recruitment for both SCD and β-thalassemia trials is now underway. Correctseq is committed to advancing CS-101 — a first-in-class, China-originated gene-editing therapy — to deliver safe, effective, and accessible treatments for patients worldwide living with severe hemoglobin disorders.

About CorrectSequence Therapeutics

CorrectSequence Therapeutics (Correctseq), incubated at ShanghaiTech University, is dedicated to leveraging innovative gene-editing technologies to transform the lives of people with severe diseases. The company has developed multiple state-of-the-art base-editing systems that offer exceptional precision, minimize off-target effects, and enhance in vivo editing efficiency. Correctseq’s mission is to discover, develop, manufacture, and commercialize curative genetic medicines across a broad range of conditions. Its robust pipeline spans genetic disorders, metabolic diseases, and cardiovascular conditions, with several programs already advancing toward clinical development.

For more information, visit www.correctsequence.com.

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

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，多位海内外β-地中海贫血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。