Develop Innovative Base Editing System and Nearly 10 Pipelines, 1st Pipeline be IND Ready By 2023

Recently, CorrectSequence Therapeutics (Correctseq), a biotechnology company aims to use their own innovative gene editing system to help people living with serious diseases, announced that transformer Base Editor (tBE) developed independently is authorized by USPTO (United States Patent and Trademark Office) formally and became the Chinese first base editing tool authorized by overseas patents.

tBE is a new Base Editor tool which is developed by the scientific co-founders of Correctseq. 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. 

Previously Correctseq already had a new base editor called eBE, which is the first base editing tool authorized by Chinese patents.

Dr. Xiaodun Mou, CEO of Correctseq, was invited by SciPhi. She introduced the significance of the overseas patent authorization of tBE and shared the current R&D plan of Correctseq. 

Figure 1: Dr. Xiaodun Mou, CEO of Correctseq 

“tBE becomes the first Chinese self-developed base editing tool authorized by overseas patents, which not only fills the patent gap of domestic base editing companies in overseas markets, but also has great significance for the company's future global layout.” Dr. Xiaodun Mou said.

Dr. Xiaodun Mou joined Correctseq as CEO in 2021. She obtained her Ph.D. in Chemical Biology from Rensselaer Polytechnic Institute, and B.S. in Chemistry from Fudan University. Dr. Mou 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. She was experienced in mAb, ADC, mRNA, VLP, AdV, AAV in therapeutic and preventive treatment, vaccine, CGT, rare disease. Dr. Mou was served as the Vice President in WuXi Biologics Development and Manufacturing and the Site Head of Hangzhou, China and worked on drug development in Pfizer’s BioTherapeutics division (US) and in Merck (MSD US). 

Correctseq based in Zhangjiang, Pudong district, Shanghai, has multiple patents for base editing systems. Multiple pipelines for genetic diseases, tumor immunotherapy, metabolic diseases, and infectious diseases are well underway. The first IND pipeline for thalassemia is developed fast. So far, Correctseq has raised more than 300 million yuan in total and is currently conducting a B round of financing.

Aug 2020, Prof. Jia Chen, Prof. Li Yang, Prof. Hao Yin and Prof. Bei Yang co-founded Correctseq. They plan to transform the scientific research results of gene editing field into industry products and develop innovative base editing therapy.

They aims to use the innovative gene editing system to help people living with serious diseases. The Base Editing technology can solve the safety problems of CRISPR/Cas9. It will realize editing the gene precisely through correcting one mutated base gene, without making double-stranded breaks in the DNA. Base Editor turns a scissor into a pen. 

(Source from：Howard Hughes Medical Institute)

Dr. Mou introduced, the scientific co-founders of Correctseq have developed multiple base editing system, including eBE, dCpf1-BE, hA3A-BE, BEACON, tBE, etc.

Among these base editing tools, eBE is the first base editor developed by the scientific co-founders in 2017, which is a higher and more efficient enhanced Cas9 base editor (Cell Research, 2017). It produces fewer by-products and has fewer random nucleotide insertions and deletions, which is suitable for the indications requiring more precise editing. In 2018, they developed a dCpf1 base editor (dCpf1-BE) for efficient editing within the genome A/T-enriched region (Nature Biotechnology, 2018a) and a universal Cas9 base editor hA3A-BE with efficient editing in G/C-enriched region and hypermethylated region (Nature Biotechnology, 2018b). In 2020, they developed the dCas12a base editor (BEACON) that does not activate the DNA damage response pathway or p53 pathway (Cell Reports, 2020), it’s safer for cells. 

the transformer Base Editor (tBE) which is authorized by USPTO now was developed in 2021.  Dr. Mou introduced, tBE is the best base editor for controlling off-target mutations and editing on-target among all cytosine base editors. tBE exhibits higher accuracy and security. It has a specific design and can edit in GC-enriched region and hypermethylation sites, controlling both gRNA-dependent and gRNA-independent off-target mutations which could occur during editing by regular BE (Nature Cell Biology, 2021).

“tBE likes a “Transformer” which is flexible to suitable for many kinds of deliver methods such as AAV, mRNA/LNP. This will realize efficient delivery in vivo.” Said Dr. Mou.

Figure 2: tBE system

Dr. Mou also said, Correctseq pays much attention on applying for national and overseas patents for the innovative gene editing technology. Gene editing therapy has great clinical potential in cure human genetic diseases and other serious diseases, so patents of gene editing technology are important and have big business value. It will help gene editing company enter oversea market in the future.

The scientific co-founders of Correctseq have created a series of base editing system. Correctseq has already applied for PCT (covering 15 global regions) for 7 base editing tools and applied for Chinese patents for 3 base editing tools, 2 of which have been granted Chinese patents in 2020 and 2021.

“These base editors’ patents national and oversea will make sure the pipeline are well underway and make our company on the leading position in the base editing field.” Dr. Mou said with confidence.

Correctseq is the first company who has the Chinese base editing tool authorized by Chinese patents and oversea patents. These original base editing technologies mentioned above are the underlying core technologies for Correctseq to develop base editing therapies.

Dr. Mou said that these underlying core technologies have enabled the company to develop and screen effective therapeutic targets for a variety of genetic diseases or rare diseases over a long period of time. She believes that the therapeutic potential of these tools could be explored in hereditary diseases of the blood system or rare diseases, ophthalmology, metabolic hereditary diseases of the liver, etc.

According to its website, the company is building a new drug discovery platform based on tBE and other base editing systems and nearly 10 pipelines based on the drug discovery platform for genetic diseases, tumor immunotherapy, metabolic diseases, and infectious diseases are well underway. At the same time, Base Editing technology can be applied on cell and gene therapy, antibody and ADC drugs, to control the immune response effectively and improve the therapeutic effect.

Figure 3: Correctseq's portfolio

The first IND pipeline is for thalassemia, using tBE to create a new precise base editing therapy. According to Dr. Mou’s introducing, compared with Cas Nuclease gene editing therapy, tBE exhibits undetected off-target mutations, higher editing efficiency and γ-globin induction, and lower cytotoxicity. The tBE therapy for thalassemia has the potential to be a BIC gene editing therapy.

“Our 1^st IND enabling pipeline for thalassemia will be IND ready by 2023, our R&D plan is made according to this timeline.” Said Dr. Mou.

Dr. Mou added, in the next 3-5 years, Correctseq will focus on pushing the first pipeline into IND, meanwhile pay attention on developing new pipelines and the advancement of other pipelines. At present, Correctseq have nearly 10 pipeline underway and is establishing an efficient IND declaration system and a quality system with global quality standards as soon as possible and accelerate the IND declaration of each pipeline.

Meanwhile, Correctseq has set up R&D and manufacturing centers in Shanghai and Zhangjiang Cell Industrial Park, as well as the regulatory and clinical center in China Central Place, Beijing. The R&D laboratory, CMC process development laboratory, and cGMP manufacturing facility are built with world-class standards, which strongly guarantees the rapid translation and application of the innovative research.

Reference links:

1.https://mp.weixin.qq.com/s/jwwJ0QhHLkAfXRi5H5Phrw
2.https://www.nature.com/articles/s41556-021-00671-4
3.https://www.nature.com/articles/cr2017111
4.https://www.nature.com/articles/nbt.4102
5.https://www.nature.com/articles/nbt.4198
6.https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30700-2？_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124720307002%3Fshowall%3Dtrue

(Thank SciPhi for its attention and report on Correctseq)