Xuanjing Bio Secures Over RMB 100 Million in New Financing, Achieves Breakthroughs in Both Liver-Targeted Pipeline and Extrahepatic Delivery

36Kr learned that Rigerna has completed an angel+ round of financing exceeding 100 million yuan. This round of financing was jointly led by Shanghai Science & Technology Investment Co. Ltd and Qihang Capital, with participation from Suzhou Xincheng Private Equity Fund Management Co., Ltd., Jinhua United Runpu, and Yuanxi Haihe (Tianjin) Biomedical Industry Fund Partnership (Limited Partnership). Existing shareholder Beijing Baixun Investment Management Co., Ltd. also increased its investment. The proceeds from this round of financing will mainly be used for the clinical research of the company's first siRNA drug RG002C0106, the advancement of multiple preclinical pipelines, as well as the rapid development of non-liver tissue in vivo delivery technology and corresponding pipelines. Meanwhile, since its establishment, Rigerna has completed two rounds of financing totaling over 200 million yuan.

Rigerna was founded in 2022, focusing on the research and industrialization of small nucleic acid drugs. Dr. Huang Yuanyu, the founder, has over 16 years of experience in the field of nucleic acid pharmaceuticals. He has worked for leading small nucleic acid pharmaceutical companies for many years, leading the establishment of multiple small nucleic acid pharmaceutical technology platforms and the development of a series of small nucleic acid drugs, successfully advancing five siRNA drugs into Phase I-II clinical trials. The company's core team has more than 10 years of experience each, covering the entire process including nucleic acid biology, nucleic acid chemistry, drug delivery, project management, CMC research, regulatory submissions, and clinical development.

Small nucleic acid drugs are one of the rapidly emerging fields in the biopharmaceutical industry in recent years. Especially after the COVID-19 pandemic, as the market performance of mRNA-based drugs driven by mRNA vaccines has declined, investment enthusiasm for RNA therapies has further shifted towards the more mature, predictable, and commercially promising small nucleic acid sector. In 2023 alone, there were approximately 20 financing events for small nucleic acid drug projects, primarily involving siRNA and ASO.

In simple terms, small nucleic acid drugs (including siRNA and ASO) must go through multiple steps such as systemic circulation, organ targeting, cellular uptake, and endosomal escape to take effect in the human body. In this process, first, unmodified small nucleic acids are inherently unstable; moreover, they only function inside the cytoplasm or nucleus, leading to challenges like low delivery efficiency. To address the former, sophisticated chemical modifications can be employed; for the latter, ligand conjugation or other delivery systems must be utilized to overcome these obstacles.

In other words, the development of small nucleic acid drugs is a comprehensive and systematic issue, where nucleic acid sequences, chemical modifications, and delivery carrier technologies are all indispensable.Rigerna has carried out a comprehensive layout and built three technology platforms with independent intellectual property rights, including the nucleic acid sequence design and screening platform RIHOST®, the chemical modification platform RICMO®, and the in vivo delivery platform LICOD®.

Among them, delivery technology is currently the focus and key competitive point for small nucleic acid pharmaceutical companies worldwide. In Huang Yuanyu's words, the development of delivery technology is the foundation upon which Rigerna "sets sail" and the core skill to "journey far."

From the two major delivery directions of intrahepatic and extrahepatic, Rigerna's LICOD® delivery technology has simultaneously laid out relevant R&D. Among these, in the relatively mature liver-targeted delivery technology, Rigerna has also established GalNAc conjugation technology. However, unlike the well-known "trident" structure familiar to peers, Rigerna has designed a new generation of GalNAc conjugation structure, which offers numerous advantages such as fewer synthesis steps (a 70% reduction compared to leading competitors' carriers), lower production costs, high delivery efficiency, and flexible conjugation methods.

In the development of extrahepatic delivery technology, a common challenge in the field is how to identify and confirm ideal receptor molecules for cellular entry, as well as design and screen efficient and safe ligand molecules based on these receptors. In this regard, Huang Yuanyu believes:"Do not expect to find a combination like GalNAc-ASGPR that scores a 'perfect 100' in extrahepatic tissues in the short term. Instead, from the perspective of drug development, it is more important to adopt a product-oriented mindset to establish extrahepatic delivery technologies. In other words, as long as the delivery technology meets the various dimensional requirements of drug development, it is sufficient. Or, the extrahepatic delivery technology we pursue only needs to score '70 or 80'."

Currently, Rigerna has completed the development and validation of delivery carriers for seven types of extrahepatic tissues, including kidneys, muscles, fat, heart, central nervous system, lung tissue, and eye tissue, based on multiple proprietary strategies. The efficacy and long-term effectiveness have also been evaluated in animal models.

Taking kidney tissue delivery as an example, Rigerna has successfully tested a series of conjugated molecules. Among them, the representative LICOD-K1 carrier achieved specific targeted distribution in rodents, with siRNA conjugates showing more than 10 times higher exposure in kidney tissues compared to non-carrier siRNA. Validation experiments were also completed in non-human primates (NHP), achieving over 70% inhibition efficiency. It is reported that the kidney-targeted delivery technology developed by Rigerna is at the international forefront.

In addition, Rigerna's two major platforms, RIHOST® and RICMO®, have been successfully established. Notably, the design and screening efficiency of the RIHOST® platform is several to dozens of times higher than traditional methods, while the RICMO® platform has completed the development and patent layout of a series of innovative "modification general formulas." "The design and screening of nucleic acid sequences, chemical modification, and in vivo delivery are three interlinked and progressive development processes that require collaboration and integration to achieve the efficient development of nucleic acid drugs."

In August this year, RG002C0106, a liver-targeted siRNA drug pipeline targeting complement C3 developed by Rigerna, has simultaneously obtained clinical approval in Australia and China, and is about to complete the dosing of the first subject.In addition, the company's liver-targeted therapies for chronic diseases such as cardiovascular and metabolic disorders are in the preclinical research stage, while the development of extrahepatic pipelines is also being actively validated and strategically planned.

Huang Yuanyu frankly stated, "The selection of pipelines must take into account various factors. The company's first pipeline has chosen a differentiated target, and this pipeline can be developed for multiple indications, including rare diseases such as C3 glomerulopathy as well as relatively more common kidney diseases like IgA nephropathy. The choice of the kidney disease field for the first pipeline allows for clinical research to be completed with fewer recruited patients compared to cardiovascular or metabolic diseases, enabling a Biotech company in its start-up phase to rapidly advance through each stage of clinical research. Meanwhile, Rigerna has also laid out multiple pipelines related to major cardiovascular and metabolic diseases, demonstrating outstanding market prospects."

In terms of external cooperation, Rigerna has attracted the attention of several international MNCs, publicly listed pharmaceutical companies in China, and Biotech firms. The company is actively exploring collaborations based on pipelines or technology platforms with these enterprises of different sizes, characteristics, and needs.

Huang Yuanyu revealed: "Small nucleic acid drugs have high drug-like properties and strong certainty, and the value of the pipeline or technology platform can be demonstrated even at the preclinical stage; therefore, at the relatively early preclinical stage, MNC companies already show strong interest in cooperation. Rigerna is efficiently and orderly advancing its work, and relevant cooperation is expected to be reached soon."