Nov 17-18, 2022, the 4th Bio-ONE Forum was hold in Shanghai. Mr. Edwin Lan, head of CMC-MFG, Ex vivo Platform of CorrectSequence Therapeutics (Correctseq), participated in the forum and made a speech titled CMC on ex vivo Platform.
Figure: The 4th Bio-ONE Forum
Mr. Edwin Lan introduced the technology and CMC of global gene therapy, taking β-thalassemia as an example. At present, there are about 30 million people carrying thalassemia gene mutation in China, and the number of patients with severe and intermediate thalassemia is about 300 thousand. β-thalassemia results from beta-globin gene mutations that impair beta-globin chain synthesis. Currently, the treatment for thalassemia is blood transfusion, which needs long-term treatment and brings risks inducing hemolysis. This treatment will cause great psychological stress and financial burden to patients. With the development of gene therapy technology, autologous stem cell transplantation has been developed to treat this disease. It can be divided into gene therapy, CRISPR/Cas9 technology-based gene editing therapy and base editing therapy according to the technical principle.
Correctseq has developed a creative precise gene editing therapy for β-thalassemia based tBE (transformer Base Editor) which was created by the scientific founders of Correctseq. Compared with Cas Nuclease gene editing therapy, tBE exhibits undetected off-target mutations, higher editing efficiency and better therapeutic effect, and lower cytotoxicity.
Mr. Edwin Lan also introduced the principle and CMC process of ex vivo gene editing hematopoietic stem cell therapy. First, it needs collecting patients' autologous hematopoietic stem cells. Then gamma-globin is reactivated with tBE technology to perform hematopoietic function. After a series of CMC processing, the edited stem cells are injected back into the patient's body, to achieve a complete cure.
At the same time, Mr. Edwin Lan compared the technology of ex vivo gene-edited hematopoietic stem cell products and autologous CAR-T products, and summarized the common challenges of the two and the special challenges of gene-edited stem cell therapy. As a creative therapy for ex vivo gene-edited hematopoietic stem cells, there are many challenges in the process such as limited number of initial cells, high requirements for preventing confusion, contamination and cross-contamination, difficulty in process characterization, and high aseptic process challenges. Correcseq actively challenges the technological difficulties of this therapy and provides corresponding solutions to ensure the safety and effectiveness of this treatment.
Figure: Mr. Edwin Lan, head of CMC-MFG, Ex vivo Platform,
made a speech titled CMC on ex vivo Platform
Figure: the principle of ex vivo gene editing therapy of Correctseq
Mr. Lan has nearly 16 years' industrial experiences in CMC development and manufacturing, China IND/BLA filing of mAb, CAR-T and sterile products, and global IND filing. Mr. Lan also has rich experience in establishing new manufacturing sites. Before joining in Correctseq, Mr. Lan served as Senior Director of JW therapeutics, MAH manufacturing head and Global MSAT (Manufacturing Science and Technology) head. He played a key role in the development and launch of the CAR-T product, Relma-cell, which is the 2nd approved CAR-T products in China. Before joining JW therapeutics, Mr. Lan worked in several MNCs, including Innovent Biologics, Baxter R&D center, AstraZeneca and Fresenius-SSPC.