Built on deep expertise in oligonucleotide chemistry, Leaderna Therapeutics is advancing a new generation of siRNA medicines for chronic diseases, with programmes spanning hypertension, dyslipidaemia and obesity. CEO Dr Jinqiao Wan discusses the scientific choices shaping the company’s evolution, its push into extrahepatic delivery and dual-target RNAi, and the clinical milestones that could define its next stage, while reflecting on China’s growing potential to compete globally in siRNA therapeutics.
How did your experience at HitGen lead to the creation of Leaderna and its focus on siRNA therapeutics?
I joined HitGen in 2012 as part of one of its earliest teams, when we were essentially starting from scratch, and spent the next 11 years leading much of the chemistry work. One of my main responsibilities was helping to establish HitGen’s DNA-encoded library (DEL) platform, particularly the nucleoside and nucleic-acid chemistry involved in designing and synthesising DNA-encoded compounds. Given the importance of oligonucleotide chemistry to DEL technology, I also helped establish HitGen’s oligonucleotide chemistry platform, which later developed into a dedicated business. By the time HitGen listed on the Shanghai Stock Exchange STAR Market in April 2020, I was Vice President of the R&D Chemistry Centre and one of its core technical personnel.
Our interest in small interfering RNA (siRNA) therapeutics had actually started around 2018, when we were closely following the progress of inclisiran, a long-acting siRNA targeting PCSK9 to lower low-density lipoprotein cholesterol (LDL-C). Its encouraging clinical results showed us that siRNA was becoming a viable therapeutic approach for chronic diseases, and we felt that the era of siRNA therapeutics was beginning. The field was also closely connected to my own scientific background, as my PhD research had focused on nucleoside and nucleic-acid chemistry, including antiviral and anticancer compounds.
After HitGen went public, we began thinking about what could come next, both for the business and for a small group of us who wanted to build something new. Although DEL and siRNA are different technologies, there was a natural connection through the capabilities we had already developed in oligonucleotide chemistry, nucleic-acid synthesis and modification, and bioinformatics. We began pilot studies in 2020 and incubated the programme within HitGen for around two years before establishing Leaderna in July 2022. By late 2022, we were operating independently, with HitGen remaining a shareholder but without controlling the business.
During that incubation period, we explored several approaches before deciding to focus our proprietary platform on siRNA. The main driver was the unmet medical need in chronic diseases, particularly cardiovascular and metabolic conditions such as hypertension, dyslipidaemia and obesity, which affect large patient populations and often require treatment over many years. We saw siRNA as particularly well suited to these diseases because of its target specificity and long-lasting activity, with the potential to reduce dosing frequency and improve treatment adherence. Advances in chemical modification and targeted delivery were also improving the stability, potency and tolerability of siRNA medicines. For us, that combination of specificity, durability and the potential for a favourable safety profile made siRNA the right technology for the chronic diseases we wanted Leaderna to address.
How has Leaderna built and differentiated its capabilities in siRNA therapeutics?
Our foundation is the experience the team had already accumulated in oligonucleotide and nucleic-acid chemistry before Leaderna was established. We complemented that expertise by recruiting Dr Jiehua Zhou, who had been my lab mate during our PhD studies at Wuhan University and later spent many years at City of Hope in the United States working on RNA biology, RNAi and targeted siRNA delivery. We initially benefited from HitGen’s infrastructure and capabilities in oligonucleotide chemistry and delivery ligands, but once Leaderna was established, we began developing our own proprietary platforms. Today, these include NEATL for siRNA modification and delivery, LOCATED for lipid-conjugate extrahepatic delivery, and DIRECT, our single-molecule, dual-target RNAi platform, which is designed to regulate two disease-related targets with one molecule. This could be particularly relevant in chronic diseases where multiple biological pathways need to be addressed.
We believe there is still considerable room to differentiate through siRNA chemistry because the design space is extremely large. Sequence selection, the pattern and position of chemical modifications, backbone design, conjugation and delivery can all affect potency, stability, specificity, durability and safety. Alnylam and Ionis are pioneers in oligonucleotide therapeutics and have established very successful technologies, but that does not necessarily mean the same chemistry will be optimal for every target or molecule. We have therefore developed our own siRNA modification chemistry and continue to explore different combinations for individual programmes. Artificial intelligence and machine learning could also help identify better combinations within this design space, provided they are supported by sufficiently large, diverse and high-quality datasets.
Extrahepatic delivery is another important area of differentiation for us. Delivery to the liver is already well established, particularly through N-acetylgalactosamine (GalNAc) conjugation, but efficiently reaching adipose tissue, the central nervous system and other tissues remains a major challenge. Our activin A receptor type 1C (ACVR1C), or ALK7, programme for obesity is one example of how we are approaching this. Several companies, including Arrowhead and Alnylam, are pursuing the same target, and a number of Chinese companies are also entering the field. Our programme remains at the IND-enabling stage, but we have developed a different delivery approach and benchmarked our preclinical results against published data from Arrowhead and Alnylam. By varying the lipid conjugate, its attachment position on the siRNA and an additional targeting moiety, we can fine-tune biodistribution to specific tissues. Our internal studies have shown encouraging durability of target suppression at comparable doses, although it is still too early to know whether this will translate into a clinical advantage.
Alongside the technology, we are continuing to build the clinical capabilities needed to take these programmes forward. We already work closely with principal investigators across China, including Professor Jiguang Wang and Ruijin Hospital in Shanghai, and are gaining clinical experience across hypertension, dyslipidaemia and metabolic disease. We have strong scientific and clinical expertise in several areas, but we recognise that the requirements change significantly as programmes move from preclinical research into larger patient studies. Strengthening our clinical development team is therefore an important part of Leaderna’s next stage.
What are the main programmes in Leaderna’s pipeline, and how are they positioned across chronic diseases?
Our overall focus is on chronic diseases rather than any single therapeutic area. If we believe strongly in a target and have the technology to address it effectively, then it is something we can consider. Today, our pipeline spans hypertension, dyslipidaemia and metabolic diseases, particularly obesity and excess body fat. In hypertension, our lead programme is LDR2402, a long-acting siRNA targeting angiotensinogen, which is now in Phase II clinical development in China. In dyslipidaemia, LDR1259 is our single-molecule, dual-target siRNA against PCSK9 and LPA, the gene encoding apolipoprotein(a), with the aim of reducing both LDL-C and lipoprotein(a). It received implied clinical trial approval from China’s Centre for Drug Evaluation in August 2026 and can now move into clinical development. We are also developing an earlier-stage siRNA targeting angiopoietin-like 4 for dyslipidaemia.
In metabolic disease, LDR2515 is our siRNA targeting inhibin subunit beta E (INHBE), which is now in Phase I development for overweight and obesity. What interests us about this pathway is its potential to reduce fat mass while preserving lean mass. We also have an ACVR1C, or ALK7, programme using our extrahepatic delivery technology to target adipose tissue, which is currently at the IND-enabling stage. These programmes address different diseases, but the underlying strategy is the same: where we see a compelling target in chronic disease and believe our siRNA chemistry and delivery technologies can address it effectively, we are prepared to pursue it.
What are the key catalysts for Leaderna’s clinical programmes, and how will they inform their future development?
There are several important catalysts for us, beginning with clinical validation of the pathways we are pursuing. In hypertension, we are closely following zilebesiran, the AGT-targeting siRNA being co-developed by Alnylam and Roche, because it targets the same biological pathway as LDR2402. It has progressed into the global Phase III ZENITH cardiovascular outcomes trial, and while the mechanism has already shown clinical proof of concept, the Phase III results will be important in determining whether sustained AGT silencing can translate into cardiovascular outcome benefits. At the same time, our own Phase II study of LDR2402 in Chinese patients with mild to moderate hypertension is an important catalyst. Recruitment has been completed, and the study should provide important efficacy and safety data in a Chinese population. Our initial focus is China, but we design our preclinical and clinical programmes according to international standards so that the data can potentially support future development and regulatory discussions with agencies such as the FDA and EMA, although bridging or multiregional studies may still be required.
Our metabolic programmes are more exploratory because the biology is less clinically validated than AGT in hypertension. LDR2515 is now in Phase I, while companies including Wave Life Sciences and Arrowhead are also investigating the INHBE pathway, so our immediate catalyst is to demonstrate that our compound is safe and biologically active in humans. What interests us most about INHBE inhibition is its potential to improve body composition, particularly by reducing visceral and other metabolically important fat while preserving lean mass, an effect for which early clinical evidence is beginning to emerge from other programmes. We are not currently prioritising metabolic dysfunction-associated steatohepatitis (MASH), although it could become relevant as our understanding of the mechanism develops.
From there, the question is how that biological effect translates into meaningful clinical benefit and where the mechanism is best positioned, whether as a standalone obesity treatment, in combination with incretin therapies, for maintenance after weight loss, or potentially in other metabolic diseases. Regulatory expectations will also shape that decision, as body-weight reduction remains the established primary efficacy measure in obesity, while body composition and muscle preservation are currently more relevant as secondary or exploratory measures.
How has Leaderna approached financing, and how do you see the investment environment for siRNA in China?
We have been quite capital-efficient since establishing Leaderna, completing several financing rounds to support the development of our siRNA pipeline and technology platforms. Most recently, in March 2026, we completed a RMB 150 million financing round led by Tao Capital and co-led by Qishen Venture Capital, with HitGen and several existing investors also participating, followed by an A+ round in August. The broader financing environment has been challenging, particularly in 2024, but sentiment began to improve during 2025 as Chinese biotech financing recovered and cross-border business development and licensing activity accelerated. The growing number of deals between Chinese biotech companies and multinational pharmaceutical companies has helped demonstrate the value of innovation coming from China, while the recovery of the Hong Kong biotech market has also strengthened investor confidence. That momentum has continued into 2026 and, particularly for innovative areas such as siRNA and other oligonucleotide therapeutics, we remain optimistic about the financing environment.
Looking ahead, what strengths could enable China to compete globally in siRNA therapeutics, and what is your long-term ambition for Leaderna?
I believe China has a real opportunity to become globally competitive in siRNA because the field is still relatively young, with a limited number of approved medicines and much less accumulated experience than more established drug modalities. I would not say that everyone is at the same starting line, as companies such as Alnylam and Arrowhead have built much deeper experience over many years, but there is still considerable room for innovation, particularly in next-generation chemistry, conjugation and extrahepatic delivery. Developing siRNA therapeutics also involves a great deal of engineering, from optimising the sequence, chemical modifications and delivery system through to manufacturing and early clinical development, and these are areas where Chinese biotech and pharmaceutical companies have become increasingly strong. Combined with China’s capabilities in clinical execution, speed of development and the broader supply chain for nucleic-acid therapeutics, I believe this gives Chinese companies a genuine opportunity to compete globally. Whether we are already better than US companies is difficult to say, but China has developed meaningful strengths in chemistry, engineering and early clinical development.
For Leaderna, the long-term ambition is ultimately very simple. Like most founders, my dream is to bring one of our own drugs to market and see patients genuinely benefit from our inventions. That is what we are working towards.
