Suzhou Ribo Life Science Co., Ltd is committed to the improvement of key technologies around siRNA therapeutic development. The liver targeting delivery technology and second-generation modification technology at the company have evolved to a level of maturation that supports rapid development of drug candidates to clinical stages. Based on the system, four compounds have been advanced into Phase II or Phase I clinical stage to date, thus have generated encouraging data about safety, efficacy, and translational properties of the system. Ribo has made significant progress in extrahepatic delivery technologies, for delivering siRNA to organs or tissues such as kidney, lung, CNS system, and tumor. In directions such as third-generation modification technology, multi-gene silencing technology, and innovative synthesis technology, Ribo has also carried out a lot of research and achieved interesting results.
Efficient and specific delivery of siRNA has been the major bottleneck for the therapeutic application of siRNA. In 2022, a full spectrum analysis of IP landscape of siRNA delivery technologies published on Molecular Therapy: Nucleic Acids has ranked Suzhou Ribo Life Science Co., Ltd as the 11th largest global patent holder, and ranked co-fifth among industrial entities listed in the top 20 siRNA delivery IP assignees. (Ref: Delivery of therapeutic small interfering RNA: The Current Patent-Based landscape. Molecular Therapy: Nucleic Acids. 2022, 29. 150-161).
The delivery systems based on the uptake of siRNA via interaction of conjugated N-acetylgalactosamine (GalNAc) with its receptor has tremendously accelerated the siRNA drug development for the treatment of diseases associated with any gene expression in hepatocytes. GalNAc-siRNA conjugates specifically bind to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes and trigger fast endocytosis of the siRNA. This can result in highly specific and highly durable enrichment of the siRNA in hepatocytes. GalNAc-based System for liver TARgeting, named RIBO-GalSTAR®, is an siRNA liver targeting delivery technology that Suzhou Ribo Life Science Co., Ltd developed independently through efforts in the past decade. The patents of RIBO-GalSTAR® have been issued by patent authorities in important territories such as China and the United States, and the technology has been employed in the research and development of a full panel of siRNA drug candidates for various targets and indications related to gene expression in the liver. Four of the drug candidates have been advanced into the clinical stages, among which one has entered the phase II clinical stage.
In addition to liver targeting technology RIBO-GalSTAR®, Suzhou Ribo Life Science Co., Ltd has for the last two years been investing great efforts and resources in the development of siRNA delivery technologies for extrahepatic tissues and organs, such as tumor, central nervous system (CNS), lung and kidney, etc. The proprietary Oncology Specific TARgeting technology, (or RIBO-OncoSTAR), enables specific drug delivery to a variety of tumors, for example. RIBO-OncoSTAR are currently being explored in glioblastoma with very positive results, which suggest a possible first-in-class treatment for this devastating disease could be on its way. RIBO-OncoSTAR will be further explored for treatment of other cancer diseases, too.
siRNA modification is a very important key technology in improving the efficiency, durability, and safety of siRNA drugs. Naked or unmodified oligonucleotides not only are highly susceptible to degradation, but also can trigger different degrees of their off-target effects and/or immunogenicity. Based on a large number of experimental results and long-term experience, it was recognized that innovative combinations of different siRNA backbone modifications, ribose modifications, base modifications, or other modifications can greatly improve the druggability of siRNA candidates. RSC2.0（Ribo Stabilization Chemistry）is based on such systematic study on the mechanisms of siRNA degradation and stabilization and their correlation with potency and/or off-target effects. Ribo's efforts in this direction have focused on continued optimization of the modification platform to support the development of siRNA drugs to address unmet medical needs.