Zheshang Securities: Commercialization of intrahepatic delivery continues to grow, extra-hepatic delivery enters registration and clinical verification

Zhitong Finance App learned that the commercialization of intrahepatic delivery of small nucleic acid drugs continues to grow, with Amvuttra's sales of US$1.902 billion in the first half of 2026, up 137% year on year, and Leqvio's sales volume of US$932 million, up 68% year on year; the key catalyst for extra-hepatic delivery in 2026-2027 is the expansion of chronic intrahepatic diseases and the release of dual-target potential. China Biotech's small nucleic acid assets are expected to achieve global value delivery. The bank believes that the small nucleic acid industry is still at a stage where clinical benefits and commercialization are equally important, and it is optimistic about companies with performance support, commercialization capabilities, and clear clinical progress.

The main views of Zheshang Securities are as follows:

Industry progress: continuous release of liver-targeted products, registration and clinical verification of extra-hepatic delivery

Commercialization of intrahepatic delivery of small nucleic acid drugs continues to grow. GalNAc delivery has been applied to hepatogenic targets such as TTR, PCSK9, and APOC3 to extend the subcutaneous administration frequency of some micronucleic acid drugs to once every quarter or six months. In the first half of 2026, Amvuttra's sales were US$1,902 million, up 137% year on year; Leqvio had sales of US$932 million, up 68% year over year.

Extrahepatic delivery progresses and differentiates. Novartis's AOC-PMO drug Del-Zota has submitted an application for DMD accelerated approval. Del-Desiran is in phase DM1III; on the CNS side, Alnylam's C16 platform has reached phase II but is still administered intrathecally, and ArrowHead's TrimCNS platform has begun to verify the ability of subcutaneous administration to cross the brain barrier.

2026-2027 key catalysis: expansion of intrahepatic chronic diseases, great potential for extra-hepatal/dual targets

1) Intrahepatic delivery (focusing on the spread of major chronic diseases):

Cardiovascular field: Lp (a) opens up new directions, and multiple Phase III data are expected to be read. Lp (a) is elevated in about 20% of people worldwide. Currently, no specific drug has been approved to lower Lp (a). Pelacarsen phase II reduced LP (a) by up to 80%, but phase III HORIZON (n=8,323) did not reach major cardiovascular endpoints, and clinical benefits are yet to be verified in subsequent studies. Olpasiran and Lepodisiran's phase III cardiovascular outcome trials are being followed up and are expected to be completed in 2028 and 2029, respectively. Furthermore, inclisiran targeting PCSK9 is expected to disclose the outcome data of studies such as Orion-4 in 2027.

Metabolism field: APOC3 enters competition for major indications. Olezarsen was approved for SHTG, and the target audience was extended to millions of patients. Ionis gave guidelines for this indication with a peak annual net sales of more than 3 billion US dollars; Plozasiran phase III achieved a reduction of about 80% in triglycerides and a 78% reduction in acute pancreatitis cases. It is planned to submit an SHTG supplement application by the end of 2026. With quarterly administration, it is expected to compete with Olezarsen once a month. ArrowHEAD's ARO-INHBE single drug decreased visceral fat by 9.9%, lean body weight increased by 3.6%, weight loss by 9.4% and liver fat decreased by 76.7% after low doses of terpotide; Plan 26H2 initiated obesity and MASH phase II.

Hepatitis B field: The world's first drug for functional treatment of chronic hepatitis B has been approved, and several small nucleic acid hepatitis B pipelines have entered phase III. 2026/8/24, GSK/Ionis ASO therapy bepirovirsen (bepravixen, trade name: Hibsago?) Approved and marketed by the Ministry of Health, Labor, and Welfare of Japan to treat adult chronic hepatitis B (CHB) patients who have been treated with nucleoside (acid) analogs for at least 6 months and meet specific viral marker standards. Bepirovirsen has now received FDA priority review and breakthrough therapy certification. The approval results are expected to be announced by October 26, 2026.

2) Extrahepatic delivery and dual targets (focusing on CNS, muscle and synergy):

CNS delivery: The CNS market for tens of millions of patients is undergoing a verification period. Proximal catalysis in 2026 mainly comes from ArrowHead's TRIMCNS platform. ARO-MAPT is expected to disclose the first human data from the end of 26Q3 to the beginning of 26Q4, focusing on verifying CNS delivery, Tau silencing, and safety after subcutaneous administration.

Muscle Delivery: Novartis' AOC platform (intramuscular delivery) drugs targeting DMD are expected to submit BLA in 2026.

Dual target mechanism: Arrowhead (ARO-DIMER-PA, PCSK9+APOC3 dual-target lipid-lowering) is expected to reveal the first batch of human data in 26Q3; Bibet (BEBT701, PCSK9+AGT dual-target lipid-lowering and hypotensive) is in phase I/II, and frontier organisms (FB7011, MASP-2+CFB dual-target complement) are pre-clinical.

Industrial upgrading: Chinese assets have global competitive strength

China's Biotech small nucleic acid assets are expected to realize global value. On the R&D side, RiboGalStar/RiboGalStar/RiboPepStar (RADS), Shengyin (GDOC), and Bibet (GDOC) have established independent delivery platforms; Haobo Pharmaceutical's AHB-137 has entered hepatitis B phase III, and Chinese biopharmaceuticals KYLO-11 and Ruibo RBD4059 have entered phase II. Recently, clinical catalysis is still mainly based on liver targeting pipelines. On the commercial side, Proview collaborated with Novartis to receive a down payment of US$160 million and a potential payment of up to US$5.2 billion; Ruibo and Madrigal collaborated to obtain a maximum potential payment of US$4.4 billion; Shengyin collaborated with Genentech to receive a down payment of US$200 million and a milestone payment of up to US$1.5 billion. Ruibo's Hong Kong stock listing and cooperation with multinational pharmaceutical companies prove that domestic small nucleic acid platforms have received phased recognition.

The small nucleic acid industry chain is evolving towards large-scale industrialization. Large varieties of chronic diseases are forcing supply chains to upgrade. In response to the pain points of poor atomic economy and high cost of traditional solid phase synthesis processes, core suppliers with phosphoramidite monomers, solid phase carriers, and large-scale CDMO production capacity will enter an explosion period.

Investment advice

The bank believes that the small nucleic acid industry is still at a stage where clinical benefits and commercialization are equally important. The bank is optimistic about companies with performance support, commercialization capabilities, and clear clinical progress. We recommend Pharmaceuticals, Kangde, China Biopharmaceuticals, Gloria, and Nanowei Technology; focus on Ruibo Biotech and differentiated pipeline companies such as Bibet and Frontier Biotech.

Risk Alerts

Clinical R&D risk; market competition risk; intellectual property risk; supply chain and production cost risk; payment environment restriction risk.