Edigene Submits China's First CRISPR Gene-Editing Therapy IND for Transfusion-Dependent Beta Thalassemia

On October 27, Boya Ji Yin announced that the Center for Drug Evaluation of the National Medical Products Administration had accepted its clinical trial application for ET-01, a gene-editing therapy product for transfusion-dependent β-thalassemia. ET-01 is an autologous CD34+ hematopoietic stem and progenitor cell injection featuring CRISPR/Cas9-mediated modification of the BCL11A erythroid enhancer.

Thalassemia refers to a group of hereditary hemolytic anemias caused by deletions or point mutations in globin genes, which partially or completely inhibit the synthesis of globin peptide chains. Based on the specific type of impaired globin chain synthesis, thalassemia is generally classified into α-thalassemia, β-thalassemia, γ-thalassemia, δ-thalassemia, δβ-thalassemia, and εγδβ-thalassemia. Clinically, the most common forms are α-thalassemia and β-thalassemia, which result from a reduced production of one of the two polypeptide chains (α or β) that constitute normal adult hemoglobin (HbA, α2β2).

Normally, within six months after birth, an individual’s hemoglobin profile shifts from being predominantly fetal hemoglobin to predominantly adult hemoglobin. However, in a small subset of patients with β-thalassemia, elevated expression of fetal hemoglobin alleviates disease symptoms. Therefore, increasing fetal hemoglobin expression through gene editing offers a therapeutic approach for the majority of β-thalassemia patients. In China, there are up to 30 million carriers of thalassemia genes, and 300,000 individuals suffer from moderate-to-severe thalassemia. Currently, there remains a substantial unmet medical need among patients with transfusion-dependent β-thalassemia.

ET-01, an autologous CD34+ hematopoietic stem and progenitor cell injection product featuring CRISPR/Cas9-mediated editing of the BCL11A erythroid enhancer, is an investigational therapy for transfusion-dependent β-thalassemia. The drug substance of ET-01 is manufactured by collecting autologous mobilized peripheral blood mononuclear cells from patients, enriching the CD34+ cell population, and editing the erythroid enhancer of the BCL11A gene using the CRISPR/Cas9 system. This clinical trial aims to evaluate the safety and efficacy of a single transplantation of ET-01 in patients with transfusion-dependent β-thalassemia.

Regarding ET-01, Boya JiYin (Beijing) Biotechnology Co., Ltd. previously presented partial data at the 61st American Society of Hematology (ASH) Annual Meeting in December 2019. The presentation highlighted the clinical-grade scaled manufacturing of ET-01, as well as preclinical in vitro and in vivo safety and efficacy data supporting its subsequent clinical trials. These data demonstrated that in ET-01, specific DNA targets in donor-derived autologous CD34+ hematopoietic stem cells were modified with high efficiency and precision, resulting in significantly elevated fetal hemoglobin levels in erythroid cells differentiated in vitro, along with a favorable safety profile in preclinical studies.

(Original text abridged)