CITIC Construction Investment: The global small nucleic acid drug industry has achieved multidimensional breakthroughs, showcasing the global competitiveness of Chinese innovative pharmaceutical companies

According to the Zhitong Finance APP, CITIC Construction Investment has released a research report stating that small nucleic acid drugs, with their advantages of targeting traditional non-druggable targets and long-lasting effects, are expected to become the third major category of drugs following small molecules and antibody drugs. Although the development process has encountered setbacks, the breakthrough of GalNAc technology in 2014 established a successful paradigm for liver-targeted delivery, greatly activating industry development. Currently, the global small nucleic acid drug industry is achieving multi-dimensional breakthroughs in commercialization profitability, indication breakthroughs, extrahepatic delivery breakthroughs, and dual-target breakthroughs. Chinese companies are keeping pace with the global industry in this wave, resonating in sync and demonstrating strong global competitiveness.

The main points of CITIC Construction Investment are as follows:

Small nucleic acid drugs are expected to become the third category of drugs

In the mechanism of action of small nucleic acid drugs, the main steps are endocytosis, endosomal escape, and gene silencing. The key points are ① receptor selection: receptor abundance, internalization rate, ② optimizing delivery systems to improve endosomal escape efficiency, ③ using chemical modifications to enhance stability, etc. The advantages of small nucleic acid drugs compared to other drug types include: rich targets, strong specificity, and long-lasting drug effects. For innovative drug companies, the advantages of small nucleic acid drugs also include: relatively high success rates in R&D, relatively fast production, and obvious platform advantages. Looking back, the development of small nucleic acid drugs has not been smooth sailing, as major pharmaceutical companies once halted development due to issues of stability and safety. The discovery of GalNAc technology in 2014 was a key milestone that activated the field of small nucleic acid drugs, establishing a "model paradigm" for the delivery technology of small nucleic acid drugs. Extrahepatic delivery represents the next broader leap.

Global small nucleic acid drug industry achieves multi-dimensional breakthroughs

① From a commercialization perspective, Amvuttra and Leqvio show the potential of blockbuster drugs, and global leader Alnylam is expected to achieve profitability this year. ② From an indication perspective, 2025-2026 will be an important verification period for indication breakthroughs, with weight loss indications expected to reach the POC moment, and CNS indications likely to gradually open up exploration, transitioning from IT to SC. ③ From a technical perspective, extrahepatic delivery is gradually breaking through. Delivery methods such as TRiM and AOC are emerging. Avidity's AOC drug Del-zota, as the first AOC drug, has outstanding efficacy and is expected to submit a BLA by the end of 2025 and be commercially launched in 2026. The dual-target technology breakthrough has led to the submission of clinical applications for the world's first PCSK9/APOC3 dual-target small nucleic acid drug.

Chinese small nucleic acid pharmaceutical companies demonstrate global competitiveness

In recent years, with the rise of small nucleic acid innovative drug companies, the domestic small nucleic acid research pipeline has accelerated growth. Chinese small nucleic acid innovative drug companies such as BoWang and RuiBo have reached BD agreements with MNCs, showcasing the global competitiveness of Chinese small nucleic acids. In terms of indications, the pipeline of Chinese small nucleic acid drugs has previously focused mainly on cardiovascular diseases and hepatitis B. In recent years, it has also begun to gradually expand into areas such as weight loss and CNS. From a technical perspective, there is currently no generational gap between Chinese and overseas small nucleic acid technologies, and there is potential for FIC and BIC in specific target indications. They are entering a period of accelerated development for FIC and BIC drugs, with expectations of a batch of new molecules entering IND by 2026-2027, likely to continue demonstrating global competitiveness Related companies in China's small nucleic acid field: Bowang Pharmaceutical (proposed listing), Shengyin Biotechnology (unlisted), Ruibo Biotechnology (proposed listing), Shiyao Group, Qianyan Biotechnology, Mabwell, etc.

Risk warning: Industry policy risk; research and development underperformance risk; sales underperformance risk; intensified market competition risk