SanegeneBio Announces Phase II Clinical Trial Initiation of SGB-9768, a First-in-Class C3-Targeting siRNA Therapeutic in China

▲ SANEGENEBIO SGB-9768 Phase II Clinical Trial Research Center Kick-off Meeting

SGB-9768 is a"The first in China and globally leading" siRNA drug targeting complement C3 under research, utilizing SANEGENEBIO's uniquely innovative next-generation GalNAc liver delivery platform to deliver to liver cells, reduces the protein expression of complement factor C3 to treat various complement-mediated diseases, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), dry age-related macular degeneration (dry AMD), paroxysmal nocturnal hemoglobinuria (PNH), and other renal and hematological disorders.

This Phase II clinical trial launch is a multicenter, open-label Phase II study evaluating the efficacy and safety of SGB-9768 in patients with primary IgA nephropathy, C3 glomerulopathy, and immune complex-mediated membranoproliferative glomerulonephritis.In December 2024, SANEGENEBIO announced positive results from preclinical and partial Phase I clinical trials of SGB-9768 at the 8th Global Complement Drug Development Summit held in Boston, USA. Trial data showed that after a single subcutaneous injection, SGB-9768 demonstrated good safety and tolerability, while a dose-dependent, significant, and sustained reduction in C3 protein levels and complement pathway activity was observed. Compared with other siRNA products targeting the same site, SGB-9768 achieved higher target protein knockdown and maintained the knockdown level for a longer duration at the same dosage. The positive results of SGB-9768 in Phase I clinical trials support its further progression to Phase II clinical trials.

The complement system is an important component of innate immunity, playing a regulatory role in adaptive immune responses and exerting crucial immune and physiological functions in the human body, protecting the body from infections and clearing dead cells and apoptotic materials. However, once the complement system is abnormally regulated or excessively activated, it can induce inflammation and damage self-tissues, causing immune injury, closely related to the occurrence and development of some hematological diseases, ophthalmic diseases, and renal diseases. Chronic kidney disease is a major public health issue globally and in China, with a prevalence rate of 10.8% in China, meaning one out of every ten adults suffers from chronic kidney disease. Most renal diseases involve complement-mediated pathogenesis, mainly including IgA nephropathy, C3 glomerulopathy, and immune complex-mediated membranoproliferative glomerulonephritis. Currently, the treatment progress for complement-mediated renal diseases is limited, and many complement-targeting drugs are still in clinical research stages, indicating significant unmet clinical needs in this field. Complement inhibition holds promise as a new therapeutic target for treating complement-mediated renal diseases, and complement C3 is a crucial component connecting upstream activation pathways and terminal pathways in the complement system. Inhibition of C3 activity has been shown to significantly suppress complement activity, making it a powerful therapeutic target for such diseases. Therefore, developing safe and effective siRNA drugs targeting complement C3 holds substantial clinical application value for complement-mediated renal diseases.

SGB-9768 is a siRNA drug independently developed by SANEGENEBIO that targets the Complement 3 (C3) protein. It utilizes the company's uniquely innovative next-generation LEAD™ GalNAc technology for delivery to liver cells, inhibiting the synthesis of C3 protein through the RNAi mechanism, thereby suppressing complement activation. It is intended for the treatment of complement-mediated kidney diseases, including adult IgA nephropathy, C3 glomerulopathy, and immune complex-mediated membranoproliferative glomerulonephritis. Preclinical trial data show that SGB-9768 can be administered once every 3 or 6 months, effectively and continuously reducing C3 synthesis. Compared with competing products, it demonstrates superior efficacy and good safety tolerance, offering advantages such as lower treatment frequency, better patient compliance, and long-lasting effects. It has the potential to become China's first and world-leading siRNA drug targeting Complement C3.