Innovent doubles down: dual advancements in push for small nucleic acid therapies

Innovent's strategic focus in the small nucleic acid arena becomes increasingly clear.

On November 10, Innovent announced the primary results from the first-in-human Phase I clinical study of IBI3016, an siRNA drug in-licensed from SanegeneBio. These results were presented in a digital poster session at the 2025 American Heart Association (AHA) Scientific Sessions. IBI3016 demonstrated preliminary antihypertensive efficacy and a favorable safety profile.

Shortly before this (October 30), Innovent also disclosed its siRNA patent WO2025223537A1, which covers the development of a small nucleic acid drug targeting INHBE.

Within half a month, significant progress has been made on both an internally developed program and an in-licensed asset, signaling a clear intensification of Innovent's research and development efforts in the small nucleic acid field.

Recently, much of the attention on Innovent has been concentrated on its GLP-1 weight-loss drug Mazdutide and the bispecific antibody IBI363. The recent consecutive advancements in its small nucleic acid drug pipeline within a fortnight undoubtedly signal to the industry that Innovent is poised to make significant strides in the small nucleic acid domain.

Innovent is a relative latecomer to the field of small nucleic acid therapies.

On December 27, 2023, Innovent and SanegeneBio announced a strategic collaboration agreement to co-develop the small nucleic acid candidate SGB-3908 for the treatment of hypertension. This marked the first appearance of small nucleic acid-related content in Innovent's official communications. Through this partnership, Innovent secured an exclusive option, allowing it to pay an exercise fee in the future for exclusive global rights to the development, production, and commercialization of SGB-3908 across defined territories. At that time, several small nucleic acid products were already on the market, and the research pipeline continued to expand.

At the time of its IPO in 2018, Innovent's R&D pipeline was primarily focused on oncology, covering targets such as PD-1/PD-L1, VEGF, and CTLA-4. Additionally, Innovent had IBI-306, a PCSK9-targeting therapy for hyperlipidemia. In August 2023, IBI-306 was approved for marketing in China for the treatment of primary hypercholesterolemia and mixed dyslipidemia, marking the beginning of tangible returns from Innovent's strategic investments in the metabolic and cardiovascular disease areas.

Shortly thereafter, as Phase III clinical trials for its blockbuster metabolic and cardiovascular candidate, Mazdutide, neared completion, Innovent began to extend its focus into new research areas. In 2023, small nucleic acids emerged as a "dark horse" in the pharmaceutical industry, attracting significant attention from numerous pharmaceutical companies. The rapid market uptake of Novartis's siRNA drug Inclisiran following its approval made innovative drug developers aware of the potential of small nucleic acid therapeutics.

Inclisiran (brand name Leqvio) was approved by the EMA in 2020 and the FDA in 2021 for the treatment of hypercholesterolemia and mixed dyslipidemia in adults. Leveraging its long-acting advantage of requiring only two injections per year, Inclisiran's sales grew rapidly. Its full-year sales were $12 million in 2021, increased to $112 million in 2022, and further rose to $355 million in 2023, demonstrating its potential to become a blockbuster drug.

While Inclisiran's sales were growing rapidly, it also successfully expanded the application of small nucleic acids from rare diseases into the chronic disease domain. This opened up possibilities for small nucleic acid drugs to target a wider range of indications. Notably, Inclisiran shares the same target, PCSK9, as Innovent's IBI-306. Its success naturally captured Innovent's attention.

To rapidly enter the small nucleic acid field, Innovent initiated a collaboration with SanegeneBio on December 27, 2023, to co-develop SGB-3908, a small nucleic acid candidate for hypertension. Innovent's technological roadmap has also continuously expanded, evolving from early-stage monoclonal and bispecific antibodies to ADCs and fusion proteins, and now venturing into small nucleic acids. It is evident that Innovent's product strategy closely follows the trajectory of cutting-edge technological advancements.

Following its partnership with SanegeneBio, two significant M&A deals occurred in the small nucleic acid space in early 2024. On January 3, 2024, Ribolia Life Science entered into a collaboration with Boehringer Ingelheim, with a total potential deal value exceeding $2 billion, to jointly develop innovative small nucleic acid therapies for liver diseases. On January 7, 2024, Argo Biopharma reached an agreement with Novartis involving multiple cardiovascular disease drugs. Novartis agreed to pay an upfront payment of $185 million, with potential additional payments totaling up to $4.165 billion.

The frequent announcement of collaborations among innovative pharmaceutical companies in the small nucleic acid field within just ten days clearly demonstrates the high level of industry excitement.

Following the collaboration with SanegeneBio, progress on the siRNA drug IBI3016 (SanegeneBio's R&D code: SGB-3908) has proceeded smoothly. On November 10 of this year, the primary results from the first-in-human (FIH) Phase I clinical study of IBI3016 were presented in a digital poster session at the 2025 American Heart Association (AHA) Scientific Sessions. Dr. Wang Fangfang from Peking University Third Hospital delivered an on-site oral presentation of the study findings.

The clinical results showed that a single dose of IBI3016 achieved a potent and sustained reduction in AGT levels, with a maximum decrease exceeding 95%. The reduction remained stable over six months, and a decrease in blood pressure was observed across all dose groups at the three-month mark. Regarding safety, IBI3016 demonstrated a favorable safety and tolerability profile over six months, with no severe adverse events (AEs) or serious adverse events (SAEs) observed, and no incidents of hypotension. All adverse events were mild to moderate and reversible. The Phase I clinical data for IBI3016 support its continued product development.

While advancing IBI3016, Innovent has also accumulated growing experience in small nucleic acid development, and its internally developed products are beginning to emerge.

On October 30, 2025, Innovent disclosed its siRNA patent WO2025223537A1. The patent involves the research and development progress of a small nucleic acid drug targeting INHBE (Inhibin Subunit Beta E).

Inhibin Subunit Beta E (INHBE) is a member of the Transforming Growth Factor-beta (TGF-β) family. INHBE is primarily expressed in the liver, functioning as a hepatokine, and has been shown to be positively correlated with insulin resistance and body mass index (BMI) in humans. Quantitative real-time PCR analysis also indicates increased INHBE gene expression in liver samples from individuals with insulin resistance.

Currently, numerous companies from China and other countries are engaged in targeting INHBE. Leading international small nucleic acid firms, Arrowhead Pharmaceuticals and Wave Life Sciences, have advanced their candidates furthest in clinical development. Among Chinese companies, participants include SanegeneBio, Rona Therapeutics, Mohua Bio, Sirius Therapeutics, and Leaderna Therapeutics. According to statistics from PharmaCube, as of December 4, 2025, there are a total of 19 small nucleic acid products targeting INHBE globally that are in Phase I/II clinical stages or the preclinical stage.

Figure 1. INHBE-targeted small nucleic acid product under research (data source: PharmaCube)

Globally, the clinical front-runner is Arrowhead's ARO-INHBE. This candidate initiated a global Phase I/II clinical study in November 2024. Prior preclinical studies on ARO-INHBE yielded promising results: 1) In cynomolgus monkey models, subcutaneous injections of ARO-INHBE at 3 mg/kg on day 1 and day 29 achieved profound knockdown of INHBE transcripts, with a duration lasting at least 85 days. 2) In diet-induced obese (DIO) and db/db mouse models, weekly administration of an ARO-INHBE surrogate significantly suppressed weight gain and reduced fat mass, while maintaining body weight and glucose homeostasis. The potential efficacy of ARO-INHBE suggests it may be promising for combination therapy with GLP-1-based weight-loss drugs, potentially reducing the required dosage of GLP-1 agents while achieving fat loss without muscle loss.

In the Chinese market, the clinical front-runner is SanegeneBio's SGB-7342. Preclinical data indicate that this candidate possesses promising lipid-lowering potential.

The design strategy of Innovent's investigational INHBE-targeting product bears close resemblance to Alnylam's AD-1708473.1 as described in patent WO2023003922. Innovent's candidate utilizes GalNac-L96 delivery technology for liver tissue targeting. This delivery system features a long-chain structure with one end conjugated to GalNac(N-acetylgalactosamine) and the other end linked to the oligonucleotide fragment.

Figure 2. GalNac-L96 Delivery System (Source: Innovent Patent)

Early data shows that Innovent's product performs better than Alnylam's similar product in terms of weight and fat mass reduction.

However, it cannot be ignored that the competition surrounding the development of small nucleic acid drugs targeting INHBE is extremely fierce, and Innovent is in a relatively backward position in terms of progress, facing significant pressure in subsequent development.

While Innovent entered the small nucleic acid field from the monoclonal/bispecific antibody and ADC sectors, starting later than companies dedicated solely to small nucleic acids, the ultimate success of a product also depends on the speed of clinical advancement and subsequent commercialization capabilities. In terms of clinical execution and commercialization, Innovent's advantages are undoubtedly significant.

In the fiercely competitive PD-1 space, Innovent has steadily grown sales of its drug sintilimab through continuous indication expansion and commercial execution. In 2024, sintilimab sales reached approximately RMB 3.8 billion, approaching the RMB 5 billion threshold. This achievement has been strongly supported by Innovent's commercial network, which includes a sales force of around 3,000 personnel covering over 5,100 hospitals across more than 320 cities in China.

This demonstrates that, despite the intense competition surrounding INHBE-targeting small nucleic acid products, Innovent still possesses the capability to stage a comeback.

In the Chinese market, no domestically developed small nucleic acid drug has been approved for marketing. The pipelines of Chinese companies that have entered Phase II clinical trials are still primarily focused on liver disease indications, with gradual expansion into the cardiovascular field. Among leading innovative pharmaceutical companies, Hengrui Pharma's HRS-5635 and Chia Tai Tianqing's TQA3038 are also siRNA products for treating chronic hepatitis B. This indicates that R&D in China's small nucleic acid field is similarly in a phase of indication expansion, where the most clinically advanced candidates are dominated by liver disease applications, while those targeting cardiovascular and metabolic diseases are mostly in early research stages. The application of small nucleic acid drugs in broader therapeutic areas is still in its early development phase.

From an R&D perspective, we believe Innovent is likely to continue launching small nucleic acid pipelines in the future; the current steps merely represent its first move into internally developed products.

The small nucleic acid industry is now entering its initial growth phase. Breakthroughs in delivery technology and the expansion of indications provide vast development space for the sector. As Wang Meng, General Manager of Youjia Bio, aptly analogized, the current development stage of the small nucleic acid field is akin to "a car entering the highway on-ramp, beginning to accelerate." Facing such an emerging technological area, it is highly probable that Innovent will continue to advance its development efforts in this field.

Reviewing Innovent's strategic moves in the small nucleic acid space, we can observe its cautious, pragmatic, and step-by-step logic: first collaborating with SanegeneBio to test the waters with one product; then developing an internally developed candidate targeting the mechanistically well-defined INHBE using the established GalNac delivery platform. With both initiatives now achieving milestone progress, Innovent may subsequently explore new targets or novel delivery technologies to continuously expand its product applications.

For new drug development, selecting the research direction is only the beginning. The true test lies in the team's execution ability—whether it can successfully develop a product and subsequently advance it through clinical stages and commercialization at a competitive pace. The fact that Innovent achieved two significant breakthroughs in the small nucleic acid field within a mere fortnight unequivocally signals to the industry its serious commitment to making substantial investments in this emerging area.