Small nucleic acids and GLP-1 drugs exhibit synergistic effects, with major players in the weight loss industry already investing in small nucleic acid drugs. While GLP-1 controls intake, small nucleic acids regulate metabolism, positioning them as a potential "golden combination" in the field of weight loss.
According to Zhitong Finance APP, Guolian Minsheng Securities issued a research report stating that small nucleic acids and GLP-1 drugs have synergistic effects, and major weight-loss companies are already deploying small nucleic acid drugs. GLP-1 controls intake, while small nucleic acids regulate metabolism, making them potentially the "golden combination" in the weight-loss field. In the future, GLP-1RA may become a key entry point in the weight-loss domain, with multinational corporations (MNCs) further investing in small nucleic acid drugs to provide comprehensive weight-loss solutions. The main small nucleic acid weight-loss targets include the INHBE target, ARO-ALK7 target, and the GeneD target targeting muscles. Chinese pharmaceutical companies are almost on par with overseas counterparts in terms of their deployment in small nucleic acid-based weight-loss indications.
The main viewpoints of Guolian Minsheng Securities are as follows:
Arrowhead announced preliminary weight-loss efficacy for two small nucleic acid drugs.
Arrowhead Company disclosed the weight-loss effects of small nucleic acid drugs targeting the INHBE and ALK7 targets, demonstrating promising initial results: ARO-INHBE achieved precise fat reduction, with an average decrease of 9.9% in fat and up to a 38.6% reduction in liver fat. Moreover, ARO-INHBE showed muscle-building potential, with single-agent treatment indicating a 3.6% increase in lean tissue.
ARO-ALK7 demonstrated dose-dependent reductions in ALK7 mRNA levels by up to 88%, confirming that the TRiM platform can suppress gene expression in adipocytes.
A single injection of ARO-ALK7 resulted in a rapid reduction in visceral fat, with a maximum decrease of 14.1% (data adjusted against placebo).
WVE-007, a small nucleic acid drug targeting the INHBE site developed by Wave Life, also showed significant weight-loss effects.
On December 8, 2025, Wave Life released Phase I data from a small sample size study showing that WVE-007, which targets liver INHBE, reduced visceral fat by 9.4% (p=0.02), total fat by 4.5%, and increased lean body mass by 3.2% (p=0.01) after three months of single-dose administration at 240mg.
Small nucleic acids and GLP-1 drugs exhibit synergistic effects, with major weight-loss companies already investing in small nucleic acid drugs. GLP-1 controls intake, while small nucleic acids regulate metabolism, making them potentially the "golden combination" in the weight-loss field. If used after GLP-1, they can maintain weight-loss effects and prevent rebound weight gain.
In November 2025, Eli Lilly and Co invested $1.2 billion in a partnership with Shengyin Biotech to advance RNAi candidate drugs for metabolic diseases using the LEAD platform, which requires only biannual injections. In September 2024, Eli Lilly invested $1 billion in HAYA's lncRNA platform to develop treatments for obesity and related metabolic disorders. On August 28, 2025, Novo-Nordisk A/S signed a $550 million collaboration agreement with Replicate Bioscience to develop innovative therapies for obesity, type 2 diabetes, and other cardiometabolic diseases.
Guolian Minsheng Securities believes that GLP-1RA may become a key entry point in the weight-loss domain, with MNCs further investing in small nucleic acid drugs to provide end-to-end weight-loss solutions. Additionally, the validation of small nucleic acids' weight-loss effects offers MNCs who missed out on GLP-1RA drugs an opportunity to re-enter the weight-loss market.
Chinese pharmaceutical companies are advancing at a pace nearly synchronous with overseas firms in the development of small nucleic acid therapies for weight loss indications.
The main three small nucleic acid targets for weight loss are: the INHBE target; the ARO-ALK7 target; and the GeneD target, which is aimed at muscle tissue. The progress in China is almost on par with global developments. Hengrui Pharma's HRS-5817, targeting INHBE, is currently in Phase I clinical trials. Innovative drug companies holding key GLP-1 products, such as Innovent Bio, have filed patents for small nucleic acid drugs targeting INHBE, which may potentially be combined or used sequentially with Marsptide in the future to leverage product synergy. Sino Biopharm's acquired company, Hejiya, owns HJY-10, a long-acting small nucleic acid drug targeting INHBE, administered once every six months or annually, with expectations to enter clinical trials by 2026.
Investment advice
It is recommended to focus on small nucleic acid companies targeting weight loss, such as Hengrui Pharma (01276), Chengdu先导 (688222.SH), Sino Biopharm (01177), Huadong Medicine (000963.SZ), Salubris (002294.SZ), Zydus Pharma (00867), Innovent Bio (01801), and Dongyang Sunshine Pharma (06887).
Risk Warning
1) National healthcare insurance policies and centralized procurement policies result in prices lower than expected; 2) Clinical progress or time-to-market falls short of expectations; 3) Uncertainty in competitive dynamics within the industry.
