As MNCs make their moves one after another and global pharmaceutical companies lay out their strategies intensively, the oligonucleotide (small nucleic acid) field is experiencing unprecedented attention and explosive growth.

According to the Insight Database from Dingxiangyuan (DXY), there are currently 364 oligonucleotide pipeline assets worldwide that have entered the application stage or beyond, an increase of over 450% compared to 2017, demonstrating an explosive surge.

Notably, the presence of Chinese companies in this field is becoming increasingly prominent. Nearly 40% of global oligonucleotide pipelines originate from China. Domestic companies not only lead in quantity but have also gained high recognition from international peers due to their core technological advantages.

In January 2026, Suzhou Ribo Life Sciences Co., Ltd. (Ribo Life Sciences) successfully listed on the Hong Kong Stock Exchange (HKEX), raising HK$2.1 billion, becoming the first oligonucleotide stock in China. This marks a breakthrough in capital market participation for Chinese innovative siRNA drug companies.

In February 2026, Ribo Life Sciences entered into a landmark collaboration with U.S.-based Madrigal Pharmaceuticals, valued at up to US$4.4 billion. The two parties will jointly develop six innovative siRNA therapies for metabolic dysfunction-associated steatohepatitis (MASH) based on Ribo Life Sciences' proprietary liver-targeting RiboGalSTAR™ platform. This marks the second major collaboration between Ribo Life Sciences and a multinational company, following a previous partnership with Boehringer Ingelheim (BI).

At a pivotal moment in the company's development, TONACEA recently sat down with Dr. Liang Zicai, Chairman and CEO of Ribo Life Sciences, a pioneer and leading figure in China's oligonucleotide pharmaceutical industry. We engaged in an in-depth discussion on the "third wave" of oligonucleotides, breakthroughs in delivery technology, global strategy, and the future of China's oligonucleotide industry.

Dr. Liang Zicai

Chairman and CEO, Ribo Life Sciences

TONACEA 01: 2026 – The Year of Oligonucleotide Breakthrough, A Battleground

The year 2025 is widely regarded as a watershed moment for the oligonucleotide pharmaceutical industry.

During that year, the number of blockbuster oligonucleotide drugs increased from one to three. For the first time, the total sales of siRNA drugs surpassed those of ASO drugs, marking a generational handover in oligonucleotide technology.

Globally, the total transaction value in the oligonucleotide field exceeded US$$36.4 billion in 2025. Novartis shocked the world with two blockbuster acquisitions: Avidity for US36.4billionin2025.Novartisshockedtheworldwithtwoblockbusteracquisitions:AvidityforUS12 billion in cash and Regulus for US$2.5 billion at a high premium.

In China, following Ribo Life Sciences' successful IPO on the HKEX on January 9, 2026, several other oligonucleotide companies have filed for IPOs. In the first quarter of 2026, three domestic oligonucleotide projects completed out-licensing deals totaling nearly US$7 billion. Additionally, Sino Biopharmaceutical acquired Hejia Biotech. These achievements underscore that China has become an unstoppable force in the global oligonucleotide industry.

The significant progress made in 2025 has led the industry to broadly predict 2026 as the "year of explosion" for oligonucleotide drugs.

This enthusiasm is not unfounded. As early as 2017, Liang foresaw the immense potential of oligonucleotide drugs and proposed, "Oligonucleotide drugs will become the 'third wave' of modern pharmaceutics."

He stated: "Between 1997 and 2025, global sales of antibody drugs grew from US$$300 million to US300milliontoUS250 billion, an 800-fold increase over more than 20 years. With oligonucleotide sales already exceeding US$$7 billion in 2025, a similar surge to US7billionin2025,asimilarsurgetoUS250 billion will also unfold in this field. The market potential for oligonucleotide drugs may even surpass that of antibodies."

In his view, if small molecules and antibodies represent the era of "analog signals" in modern pharmaceutics – based on protein stereorecognition – then oligonucleotide drugs represent the era of "digital signals" – based on mRNA sequence recognition. In this sense, oligonucleotide drugs are the greatest fruit of the genomic revolution.

Specifically, based on their foundational technological differences, oligonucleotides possess unique advantages that small molecules and antibodies cannot match:

First: The "digital recognition" of oligonucleotide drugs significantly increases the success rate from preclinical to various clinical stages, reducing drug development risk. This changes the high-risk nature of innovative drug development.

Second: The unprecedented long-acting nature of oligonucleotide drugs, with a single injection maintaining efficacy for six months, not only provides excellent compliance and competitiveness in disease treatment but also offers vaccine-grade preventive properties, revolutionizing the treatment model for chronic diseases and truly enabling "good doctors to cure before illness."

Third: Oligonucleotide drug development is fast. From target identification to IND filing, the process typically takes only 1.5 to 2 years, highlighting their high platform-based attributes.

Fourth: The target space for oligonucleotide drugs is extremely rich. There are approximately 600 known druggable targets, of which only about one third can be targeted by antibodies. However, because oligonucleotides act at the mRNA level, their potential target universe is vast, and they can treat a very broad spectrum of diseases.

These significant advantages and development potential are attracting a diverse array of players, including MNCs and biotech companies. "This field has become a genuine strategic battleground, and the number of competitors will only grow," Liang noted.

TONACEA 02: Extrahepatic Delivery: Innovation Is the Moat

The development of oligonucleotide drugs was relatively slow in its first decade, with delivery technology being the primary bottleneck. Currently, GalNAc has become the mainstream strategy for liver-targeted delivery, and in approximately 10 target areas, homogeneous competition has emerged.

Extrahepatic delivery has become the central focus of technological competition in the global oligonucleotide field. The key challenges involve identifying and utilizing receptors with high specific expression in various tissues, designing delivery vectors capable of overcoming multiple complex biological barriers, and ultimately achieving precise targeted delivery to extrahepatic tissues and organs.

Regarding this, Liang noted: "Through years of dedicated effort, we have built a systematic extrahepatic delivery platform. We have achieved technological breakthroughs sequentially in tissues such as the kidneys, heart, fat, muscle, and central nervous system. In the near future, we expect to complete the deployment of specific delivery methods for all key tissues and cells."

In March 2026, at the RNA Leaders Europe Conference, Ribo Life Sciences presented a series of its latest extrahepatic delivery achievements for the first time. The data demonstrated the broad therapeutic potential of its proprietary RiboPepSTAR™ platform in areas including the kidneys, heart, metabolic tissues, and adipose tissue.

Kidney Targeting: Specific uptake and target gene suppression in proximal tubular epithelial cells, achieving up to 80% knockdown, were observed in multiple animal models, spanning from mouse to non-human primate (NHP) models. In various disease models, including type 2 diabetes, highly efficient and specific gene silencing was measured, along with significant improvements in multiple pharmacodynamic endpoints. The first kidney-targeted drug has been advanced to the preclinical stage.

Heart Targeting: Sustained and stable suppression of targeted cardiac genes was achieved in mouse models using heart-targeted siRNA conjugates. These molecules displayed minimal impact on muscle tissue and almost no activity in the liver and kidneys, demonstrating high specificity and offering a promising precision RNAi therapeutic strategy for cardiovascular diseases.

Adipose Tissue: In NHP experiments, effective gene expression suppression, reaching up to 96%, was measured. This demonstrates robust targeting efficiency and specificity in adipose tissue, opening new therapeutic avenues for treating metabolic diseases.

In fact, breakthroughs in extrahepatic delivery are not only about technology but also about intellectual property (IP). Liang explained that, unlike the GalNAc mechanism discovered in the last century, many receptors and ligands for extrahepatic delivery are newly discovered and thus can be protected by patents. It is unlikely that a single breakthrough will allow the entire industry to quickly follow suit.

He emphasized: "Each company must build its own delivery platform. Innovation is key. The oligonucleotide industry has characteristics of 'exhaustibility' – delivery methods, ligands, receptors, and siRNA sequences are all exhaustible. This dynamic will continue to amplify the advantages of leaders, while the space for a 'me-too' model will increasingly narrow."

TONACEA 03: Focused Direction, Parallel Strategies of Claiming Territory and Deep Plowing

Confronted with the "exhaustibility" of the oligonucleotide industry, Ribo Life Sciences has adopted a dual strategy of deep focus on selected directions combined with extensive coverage of delivery to new organs.

With a primary focus on the cardiovascular and metabolic (CVM) space, Ribo Life Sciences has implemented a comprehensive coverage strategy:

Maintaining global leadership in anticoagulant/antithrombotic oligonucleotides. A core product is Vortosiran (RBD4059), the world's first siRNA drug targeting FXI, with its development progress globally leading, and next-generation products are also in the pipeline.

In the MASH area, leveraging global collaborations with BI and Madrigal, the latter being the first company globally to successfully launch a marketed MASH drug (Rezdiffra/resmetirom), which provides Madrigal with significant clinical development and commercialization capabilities.

Rapidly advancing two assets in the lipid disorders area. RBD5044 is the second siRNA drug globally to target ApoC3 to enter clinical development, currently advancing through its Phase II clinical studies in Europe and China. Meanwhile, the license to Qilu Pharmaceutical for RBD7022, a PCSK9-targeting siRNA, is expected to initiate Phase III trials in China imminently, representing the company's most advanced self-developed asset.

Furthermore, Ribo Life Sciences is extensively covering extrahepatic tissues such as the kidney, heart, and adipose tissue, creating a wide-angled coverage strategy for the CVM field.

TONACEA 04: Beyond the Watershed – The Next Chapter for Ribo Life Sciences

Reflecting on the nearly two-decade-long evolution of Ribo Life Sciences, Liang identifies 2021 and 2022 as a pivotal watershed.

In 2021, RBD1016, the first candidate developed from Ribo Life Sciences' proprietary RiboGalSTAR™ platform, entered clinical trials. It is also the first domestic anti-hepatitis B oligonucleotide drug, marking a divisional milestone for Ribo Life Sciences – the transition from a phase of technological innovation to one of rapid pipeline advancement.

In January 2022, Dr. Lin Gan (Gan Liming) joined Ribo Life Sciences as Global Head of R&D and Chief Medical Officer. Subsequently, Ribo Life Sciences established its International R&D Center in Europe, opening a new chapter in the company's global development.

From 2022 to the present, Ribo Life Sciences has advanced a total of seven assets into clinical stages, demonstrating a significantly accelerated development pace. Among these, one product is approaching Phase III, and three others are in Phase II.

Liang noted that the company's International R&D Center currently has around 50 staff members, 30 of whom have previous experience at director-level or higher within MNCs. By integrating international systems and standards with the high execution efficiency of Chinese teams, Ribo Life Sciences has forged globally competitive R&D teams, equipping it with global development experience and capabilities in the CVM field comparable to those of MNCs today.

"Speed is not the most important factor," he stated. "What matters more is getting the direction right. The combination of these experiences and capabilities, seamlessly integrated with strong technical systems and execution power, coupled with globally established BD capabilities, represents Ribo Life Sciences' greatest advantage."

Regarding the company's BD trajectory and future outlook, Liang emphasized: "We consistently aim to drive long-term value creation as our core priority. In collaborations, we place significant weight on the intrinsic value of the assets themselves and the synergistic support for value realization and commercialization that our BD partners bring. Over the next few years, as several of our pipeline assets advance into late-stage clinical development and some successfully transition to the commercial stage, we expect the company to enter a new phase of even greater value realization."

References:

China Reform Fund, [Exclusive Interview] Ribo Life Sciences' Liang Zicai: Differentiated Innovation in China's Oligonucleotide Drugs Has Achieved Breakthroughs | New · Ecosystem

Archimedes Biotech, FXI Oligonucleotide: A Game Changer!

Ribo Life Sciences, Ribo Life Sciences' RiboPepSTAR™ Platform Achieves Precise Extrahepatic siRNA Delivery to Multiple Organs

TONACEA, US$4.4 Billion! Ribo Life Sciences and Madrigal Enter into Global Exclusive License Agreement | Member News

Ribo Life Sciences 2025 Annual Results Announcement