"Xuanjing Bio" completes a new financing of over 100 million yuan, achieving breakthroughs in both liver-targeted pipelines and extrahepatic delivery. | 36Kr exclusive.
36Kr has learned that Xuanjing Biotech has completed an angel + round of financing of over 100 million yuan. This round of financing is jointly led by Shanghai KeTou Co., Ltd. and Qihang Investment, with Xincheng Fund, Jinsha River United Runpu, Yuanxi Haihe, etc. as co-investors, and Sanyi Chuangxin Investment, an old shareholder, has made an additional investment. 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, and the rapid development of in vivo delivery technology in non-liver tissues and the corresponding pipelines. At the same time, since its establishment, Xuanjing Biotech has completed a total of two rounds of financing totaling over 200 million yuan.
Xuanjing Biotech was founded in 2022, focusing on the research and development and industrialization of small nucleic acid drugs. The founder, Dr. Huang Yuanyu, has been dedicated to the field of nucleic acid pharmaceuticals for more than 16 years. He once worked in a leading small nucleic acid pharmaceutical company for many years, leading the establishment of multiple small nucleic acid pharmaceutical technology platforms and the research and development of a series of small nucleic acid drugs, and has promoted 5 siRNA drugs into clinical Phase I-II studies. The core team of the company has more than 10 years of experience, covering the entire process including nucleic acid biology, nucleic acid chemistry, drug delivery, project management, CMC research, registration and declaration, and clinical development.
Small nucleic acid drugs are one of the rapidly emerging tracks in the biomedical industry in recent years. Especially after the COVID-19 pandemic, as the market performance of mRNA-based drugs driven by mRNA vaccines has declined, the investment enthusiasm for RNA therapy has further flowed to the small nucleic acid field with a higher degree of maturity, stronger certainty, and a clearer business prospect. In 2023 alone, there have been about 20 financings for small nucleic acid drug projects mainly including siRNA and ASO.
In simple terms, if small nucleic acid drugs (including siRNA and ASO) want to exert their effects in the human body, they need to go through multiple links such as in vivo circulation, organ targeting, cell uptake, and intracellular escape. In this process, first, the unmodified small nucleic acid itself is not stable enough; moreover, it only takes effect in the cytoplasm or nucleus, so there are problems such as low delivery efficiency. For the former, it can be solved by using sophisticated chemical modifications; for the latter, it needs to be overcome through ligand conjugation or other delivery systems.
In other words, the development of small nucleic acid drugs is a comprehensive and systematic problem, and the nucleic acid sequence, chemical modification, and delivery vector technology are all indispensable. Xuanjing Biotech has made an all-round layout and established 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 the focus and the key to competition for small nucleic acid pharmaceutical companies worldwide. In Huang Yuanyu's words, the development of delivery technology is the foundation for Xuanjing Biotech to "set out" and the core skill for "going far".
From the two major delivery directions of intrahepatic and extrahepatic, Xuanjing Biotech's LICOD® delivery technology has simultaneously arranged related research and development. Among them, in the relatively mature liver-targeted delivery technology, Xuanjing Biotech has also established the GalNAc conjugation technology, but different from the "trident" structure familiar to peers, Xuanjing Biotech has designed a new generation of GalNAc conjugation structure, which has many advantages such as fewer synthesis steps (reducing by 70% compared to the competitor carriers of leading enterprises), low production cost, high delivery efficiency, and flexible conjugation methods.
In the development of extrahepatic delivery technology, the common difficulty in the field is how to find and confirm the ideal receptor molecule for mediating endocytosis, and to design and screen efficient and safe ligand molecules based on this receptor. In this regard, Huang Yuanyu believes: "Don't expect to find a combination like GalNAc-ASGPR that can score 'a hundred points' in the extrahepatic tissue in the short term. Instead, from the perspective of drug development, an extrahepatic delivery technology should be established with a product thinking, that is, as long as this delivery technology can meet the requirements of various dimensions of drug development. Or rather, the extrahepatic delivery technology we pursue can score 'seventy or eighty points'."
Currently, Xuanjing Biotech has completed the development and verification of delivery vectors for 7 extrahepatic tissues including kidney, muscle, fat, heart, central nervous system, lung tissue, and eye tissue based on a variety of the company's unique strategies, and has completed the evaluation of effectiveness and long-term efficacy in animals.
Taking kidney tissue delivery as an example, Xuanjing Biotech has successfully tested a series of conjugation molecules. Among them, the representative LICOD-K1 vector has achieved specific targeted distribution in rodents, and the exposure of the siRNA conjugate in kidney tissue is more than 10 times higher than that of the siRNA without a carrier; and the verification experiment on non-human primates (NHP) animals has been completed, obtaining an inhibition efficiency of more than 70%. It is reported that the kidney-targeted delivery technology developed by Xuanjing Biotech has been at the international forefront.
In addition, the two major platforms, RIHOST® and RICMO®, of Xuanjing Biotech have also been established. It is worth mentioning that the design and screening platform of RIHOST® has improved the efficiency by several times to dozens of times compared to the traditional method, and the RICMO® platform has also completed the development and patent layout of a series of innovative "modification formulas". "Nucleic acid sequence design and screening, chemical modification, and in vivo delivery are three interactive and progressive development processes, and only by collaborating and integrating can the efficient development of nucleic acid drugs be completed."
In August this year, the liver-targeted siRNA drug pipeline RG002C0106 for complement C3 under Xuanjing Biotech has simultaneously obtained clinical approval in Australia and China, and is about to complete the administration of the first subject.
Huang Yuanyu said, "The selection of pipelines needs to consider various factors comprehensively. The company's first pipeline has chosen a differentiated target, and this pipeline can be developed for multiple indications, including both rare diseases such as C3 glomerulopathy and relatively high-incidence kidney diseases such as IgA nephropathy. Choosing the kidney disease field for the first pipeline, compared with the cardiovascular disease and metabolic disease fields, fewer patients need to be recruited to complete the clinical study, so as a biotech company in the start-up stage, it has the ability to quickly advance the clinical studies in each phase. At the same time, Xuanjing Biotech has also arranged multiple pipelines for major diseases related to cardiovascular metabolism, with outstanding market prospects."
In terms of external cooperation, Xuanjing Biotech has attracted the attention of many international MNCs, domestic listed pharmaceutical companies, and Biotechs. The company is actively discussing cooperation based on pipelines or technology platforms with these enterprises of different scales, characteristics, and needs.
Huang Yuanyu revealed: "The druggability of small nucleic acid drugs is high, and the certainty is strong. The pipeline value or technology platform can be demonstrated in the preclinical stage. Therefore, in the relatively early preclinical stage, MNC companies have a strong interest in cooperation. Xuanjing Biotech is carrying out work efficiently and orderly, and it is expected that relevant cooperation will be reached soon."