Cxi Securities: Pharmaceutical Biology — Breakthrough in Extrahepatic Delivery Technology, Broad Commercialization Prospects

Small Nucleic Acid Drugs Show Significant Advantages, Poised to Lead the Upgrade of Treatment Paradigms. Small nucleic acid drugs act on pre-mRNA or mRNA within cells based on the principle of base complementary pairing, achieving therapeutic purposes by regulating protein expression. Compared with small molecule and antibody drugs, small nucleic acid drugs boast abundant targets, high specificity, enhanced safety, longer-lasting efficacy, and higher R&D success rates, making them a potentially disruptive new mainstream therapy following small molecules and antibodies.

Breakthrough in Extrahepatic Delivery Technology for Small Nucleic Acid Drugs Extends Indications to Chronic Disease Field with Broad Commercial Prospects. Delivery technology plays a crucial role in the efficacy and safety of small nucleic acid drugs. GalNAc delivery technology is the mainstream strategy for intracellular hepatic delivery, successfully contributing to the approval and market launch of six siRNA therapies. It has advantages such as subcutaneous injection administration, a duration of action lasting several months, and efficient targeting of the liver, but it has tissue limitations. Drawing on the technical approach of GalNAc delivery, leading overseas small nucleic acid companies like Avidity, Arrowhead, and Alnylam have developed extrahepatic delivery technologies such as AOC, TRiMTM, and C16, successfully achieving targeting of tissues such as the lungs, muscles, central nervous system, and fat, significantly expanding the range of applications for small nucleic acid drugs. With breakthroughs in extrahepatic delivery technology, the indications for small nucleic acid drugs have expanded from rare diseases to chronic disease areas such as lipid-lowering, blood pressure reduction, and weight loss, demonstrating broad development prospects. According to statistics and forecast data in the Hong Kong Stock Exchange prospectus of Ribo Biotech, from 2024 to 2029, the global small nucleic acid drug market size is expected to grow from $5.7 billion to $20.6 billion, with a compound annual growth rate of approximately 29.40% during this period. Additionally, the activity of small nucleic acid drug transactions has increased, resulting in several significant deals. For example, in October 2025, Novartis acquired Avidity Biosciences, a leader in the AOC (antibody-oligonucleotide conjugate) field, for $12 billion; in September 2025, Novartis again partnered with Bo Wang Pharma to collaborate on multiple cardiovascular target siRNA assets, with a total transaction value exceeding $5.3 billion.