PHARMCUBE Colum | Dr. Xiaodun Mou: Base Editing Therapy is Expected to Open a New Chapter of Disease Treatment

Interviewee: Dr. Xiaodun Mou, CEO of CorrectSequence Therapeutics (Correctseq)

Market Segment: Base editing therapy

Dr. Xiaodun Mou received a doctorate degree in Chemical Biology from Rensselaer Polytechnic Institute, Troy NY, U.S.A. and bachelor’s degree in Chemistry from Fudan University. She has nearly 20 years industrial experience in CMC development and commercial manufacturing, quality, supply chain and new business establishment starting from 0 to 600 pl. Experienced in mAb, ADC, mRNA, VLP, AdV, AAV in therapeutic and preventive treatment, vaccine, CGT, rare disease. Served as the Vice President in WuXi Biologics Development and Manufacturing and the Site Head of Hangzhou, China, the senior scientist and project lead in Pfizer’s BioTherapeutics division (US) and the principal scientist and analytical leader of new and enabling technologies and CMC leader for BioProcess Development in Merck (MSD US).

01、Review 2022

As one of the most important technologies in the field of life science in the 21st century, gene editing technology is gradually showing its application potential and vigorous development. According to the data, the global genome editing market is expected to reach $4.3 billion in 2022 and $12.8 billion in 2027. The global genome editing market is expected to grow at a compound annual growth rate of 24.7% in 2022-2027.

Among many gene editing technologies, base editing technology has attracted more and more attention due to its advantages of more safety and higher editing efficiency. The field of base editing therapy is expanding to not only genetic and non-genetic diseases, but also rare and common diseases, including genetic diseases, tumors, metabolic diseases, infectious diseases, and so on.

§ 2022 Achievements of Base Editing

There are many milestone breakthroughs in the field of base editing therapy in 2022. Firstly, many clinical trials with base editing technology begun in 2022. The diseases include leukemia, sickle cell disease, beta-thalassemia, and familial hypercholesterolemia. Secondly, tBE (transformer Base Editor) created by the science co-founders of Correctseq was authorized by overseas patents, which will make Correctseq more competitive in the field of base editing therapy. Thirdly, in May 2022, the National Development and Reform Commission issued the "14th Five-Year Plan for Bio-Economic Development"，which clearly stated that it will promote the integration of advanced technologies such as genome editing and biological drug research and development as one of the important deployments to cultivate the pillar industry of biological economy.  

§ 2022 Achievements of Correctseq

There is a very important change for Correctseq in early 2022. We have developed transformer Base Editor (tBE) from Bench to Bedside, established target screening, Pre-IND and CMC platform in line with international drug regulatory standards, and successfully established and expressed tBE with suitable molecular types and complete CMC processes. Animal studies have been carried out through ex vivo cell editing and in vivo delivery (LNP and AAV), and the safety and efficacy have been verified. The first pipeline will officially enter the IND phase in 2023.

At the same time, tBE has demonstrated its powerful potential in a wider range of diseases. These disease areas include rare diseases, T cell engineering, infectious diseases, and immunooncology. tBE has demonstrated high editing efficiency for potential targets without any off-target phenomenon. Currently, we have applied for patents for targets related to these diseases, and we will gradually carry out clinical applications in these therapeutic areas in the future.

What’s more, tBE is authorized by USPTO (United States Patent and Trademark Office) formally in July 2022. It’s the Chinese first base editing tool authorized by overseas patents. Correctseq has always attached great importance to applying for national and overseas patents for R&D technology. Among the 5 series of base editing system created by the scientific co-founders of Correctseq, four have been patented in PCT covering 15 global regions.

02、Challenge and Opportunity

Gene editing technology has developed from ZFNs (zinc-finger nucleases) , TALENs (transcription activator-like effector nucleases) to CRISPR/Cas9, BE (base editing) and PE (prime editing). With the development of gene editing technology, editing efficiency and safety have been continuously improved, and application fields have also been continuously expanded. In the future, the breakthroughs include reducing off-target activity, expanding targeting range, and improving in vivo editing and delivery efficiency. For clinical applications, safety is the biggest concern. Secondly, as an innovative therapy, the effectiveness and delivery efficiency are also the key points.

§  Advantages of tBE

tBE, developed by the scientific co-founders of Correctseq, exhibits undetected off-target mutations, high editing and delivering efficiency. It connects a deoxycytidine deaminase inhibitor(dCDI) and a split TEV protease and has a specific design which will make tBE locate in target mutation and start editing. If tBE locates off-target mutation, its editing function will invalid. This brings not only no off-target mutation bus also the high efficiently editing. Meanwhile, tBE likes a “Transformer” which is flexible to suitable for many kinds of deliver methods such as AAV, mRNA/LNP. It can edit multi-targets efficiently at the same time. tBE is the best base editor for eliminating off-target mutations and editing on-target among the cytosine base editors. In clinical applications, tBE exhibits efficiently editing on multiple drug targets in animals, while ensuring safety without off-target.

03、Look Forward to the Future

Looking forward to the future, more and more innovative therapies in the field of gene editing/base editing will enter the clinic. The first pipeline of Correctseq will be IND application stage in the middle of 2023, and human trials will be conducted by the end of 2023. We are honored to be part of this transformative breakthrough in human medical development.

As time goes on, we also believe that gene editing/base editing therapy will become more and more mature, and national regulators, doctors and patients will have a more comprehensive understanding of gene editing/base editing therapy, including the principle, effect and safety, and will be more receptive to it.

§  In 3-5 years, the first base editing drug is expected to be approval.

The mission of Correctseq is to use innovative base editing technology to help people with severe disease. In the next 3-5 years, we expect the first base editing drug to be approval, helping people with genetic diseases and rare diseases. In addition, our pipeline through cell editing and direct injection for non-hereditary diseases and common diseases will gradually enter the IND application stage.

Meanwhile, we hope to share base editing technology with more partners. We can help our partners develop new pipelines and replace existing ones for targets and diseases that are not yet covered by Correctseq. For the pre-IND and IND pipeline that Correctseq has already laid out, we expect to collaborate with our partners to promote the new drugs to the clinic and market in different countries and regions at the same time. Correctseq has developed and patented many new drug targets for different diseases, such as hematological diseases, tumor immunity, infectious diseases and metabolic diseases, which involve the patients from millions to hundreds of millions. We hope to cooperate with various innovative pharmaceutical companies from different therapeutic fields, so that innovative base editing therapies can be more widely used.