On November 18, 2024, Dr. Zhiwei Yang, the founder of SiranBio, gave an oral presentation on the latest pre-clinical results of SA1211 in the 2024 AASLD meeting at San Diego, California.  SA1211 is a dual-targeting siRNA which can activate acquired immune response in addition to directly eradicate hepatitis B virus, and thus prevent viral rebound after the end of treatment. 

Using current medications, more than 95% of patients will relapse after the treatment stops.  The goal for the development of next generation CHB drugs is to achieve functional cure, which means after a definite period of treatments, the hepatitis B virus (HBV) is cleared, and no viral rebound within 24-48 weeks. Dozens of new drugs have been in clinical trials in the past few years.  No single molecule can achieve functional cure in high percentage, and several combo treatments achieved better results.

SA1211 is the first dual-targeting siRNA for the functional cure of CHB.  It is likely going to be the first dual-targeting siRNA ever in clinical trials.  SA1211 connected two siRNA molecules into a dimer, and totally kept their individual potency.  The first siRNA targets HBx, which will actively degrade the mRNA of HBV; the second siRNA targets PD-L1, which releases immune check point and allows the adaptive immunity for HBV get restored. To build the dimer, SiranBio developed a series of proprietary technologies, including Stork-L for liver targeting, Stork-W for dimerization, and eSafe for off-target mitigation.    

SA1211 shows the potency of combo treatment using one molecule. In humanized AAV-HBV mouse model, HBsAg and HBV DNA got cleared in 80% animals without viral rebound.  Very high level of antibody for HBsAg was detected in the functional cured mice. CD3+ and CD8+ T cells were significantly elevated.  This is one of the best pre-clinical result for all published CHB functional cure efforts.

SA1211 is under pre-clinical development.  IND will be filed by the end of 2025 Q1.  We expect it will get high percentage functional cure in mono-treatments, and will effectively prevent viral rebound when combined with other drug, such as ASO.  Based on our dual-targeting technology, SiranBio will develop series of siRNA dimers to treat more chronic diseases.

About AASLD:

AASLD is the leading organization of scientists and health care professionals committed to preventing and curing liver disease. It fosters research that leads to improved treatment options for millions of liver disease patients. It advances the science and practice of hepatology through educational conferences, training programs, professional publications, and partnerships with government agencies.

About SiranBio:

SiranBio is a biotech company specialized in siRNA drug development. Our core team is consisted of top scientists and pioneers of siRNA drugs in China. We have developed comprehensive and proprietary platform technologies which encompass the whole process of siRNA drug development, and established a robust pipeline with potentials to become First-in-Class (FIC) and Best-in-Class (BIC) siRNA therapeutics for several important therapeutic areas, including viral infection, metabolic diseases, and chronic pain.  Our mission is to innovate for best siRNA drugs, and treat chronic diseases for better health.