The development of cell and gene therapy is in full swing, and the enthusiasm for clinical development is high. CGT can overcome the limitations of the regulation of traditional small molecules and antibody drugs at the protein level, and can realize the upgrading of therapy or the treatment of rare diseases by means of gene expression, silencing or in vitro modification at the molecular level. With the gradual maturity of gene editing, vector transformation and other technologies and the listing of related products, the investment and financing in the field has increased rapidly, and a large number of drugs under research have entered the clinic. According to asgct data, as of October 2021, there were 1890 CGT research projects (less than 400 in 2015 from preclinical to registration), of which nearly 30% are in the clinical stage, and the indications cover cancer (mainly car-t and tcr-t) For rare diseases, ad and Parkinson’s disease (mainly gene therapy), the number of drugs on the market is expected to exceed 100 around 2030 (calculated by 20% clinical success rate).
CGT has a strong willingness to outsource production, and cdmo giants are expected to share a broad market. Due to complex technical mechanism, high threshold process development and large-scale production, strict regulatory requirements and limited industrialization experience, CGT products rely more on cdmo than traditional pharmaceuticals, and its outsourcing penetration rate exceeds 65%, far exceeding 35% of traditional biological agents. Considering that the production of virus vectors as the core involves very complex processes, extremely difficult and long preparation cycle, it is expected that the outsourcing rate of CGT will remain high in the future. According to the data exchanged by Wuxi Apptec Co.Ltd(603259) investors, it is estimated that the global CGT cdmo market will reach US $10.1 billion (five-year compound 35%) and the Chinese market will reach US $1.7 billion (five-year compound 51%) in 2025. As CXO giants such as Lonza and Wuxi Apptec Co.Ltd(603259) have relatively large production capacity and perfect GMP standards, it is expected that the dividends from the rapid development of cdmo market in the future will be shared by major giants.
Viral vector production has high barriers and complex steps. There is a large gap between supply and demand of AAV vector. Viral vector is the main delivery means of CGT at present. The mainstream includes AAV (mostly used for gene therapy) and LV (mostly used for cell therapy). Its expression production is the core of CGT drug production. The upstream of virus vector production (USP) mainly includes transfection and culture. At present, the mainstream of transfection is still the transient process of multi plasmid co transfection. In culture, the method of adherent (mature process and high titer) or suspension (large volume reactor can be used after domesticating HEK293 cells or Sf9 insect cells). Considering the expansion of production capacity, it is expected that stable transformation and suspension culture will become the mainstream in the long term (reducing cost and expanding scale). The downstream (DSP) step is more complex than biological drugs, and its yield is usually only 15-30%. According to the calculation of production model, it is expected that the gap between supply and demand of AAV carrier will be mainly reflected in commercial products (some indications have large doses); LV carrier supply can meet the needs of commercialization (less patients and small dose). A large number of car-t projects under research may affect the release of enterprise capacity.
Related enterprises. Wuxi Apptec Co.Ltd(603259) (acquired Tessa technology by acquiring oxgene), Kingsley Biotechnology (leading plasmid business), Porton Pharma Solutions Ltd(300363) (excellent team experience and rapid development), metabiology (advantage of oncolytic virus business), Pharmaron Beijing Co.Ltd(300759) (entered by acquiring absorption and Allergan Biology).
Risk warning: order acquisition is not as expected; The research and development of new technology is less than expected; Business expansion was less than expected.
