On December 10, 2024, Sanegene presented promising preclinical and phase I clinical trial results for its siRNA therapeutic, SGB-9768, targeting complement factor C3, at the 8th Complement-Based Drug Development Summit held in Boston, USA.
This drug aims to lower complement factor C3 levels to treat various complement-mediated diseases, including IgA nephropathy, C3 glomerulopathy, immune-complex-mediated membranoproliferative glomerulonephritis, dry age-related macular degeneration, paroxysmal nocturnal hemoglobinuria, and other renal and hematologic disorders. SGB-9768 is expected to become the "first in China and a globally leading" siRNA drug targeting complement factor C3.
Sanegene is conducting a randomized, double-blind, placebo-controlled, single ascending dose Phase I study in both New Zealand and China. The primary objective is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SGB-9768 in healthy subjects. The first subjects were dosed in May 2024 in New Zealand and in August 2024 in China.
As of December 1, 2024, a total of 55 subjects have been randomized to receive either SGB-9768 or placebo. Trial data indicate that after a single subcutaneous injection, SGB-9768 demonstrated good safety and tolerability. Additionally, a dose-dependent, significant, and sustained reduction in C3 levels and complement pathway activity was observed. Compared to other siRNA products targeting the same pathway, SGB-9768 demonstrates greater C3 target protein knockdown at lower doses.
Dr. Yuyan Jin, Senior Vice President of Clinical and Non-Clinical Development at Sanegene, stated: "SGB-9768 utilizes Sanegene's proprietary GalNAc liver-targeting delivery platform, which ensures excellent safety and positions us at the forefront of global innovation in siRNA therapeutics for complement-mediated diseases. The latest Phase I clinical trial data further reinforced SGB-9768's potential as a breakthrough siRNA therapy, offering new treatment options for patients with complement-mediated kidney diseases, ophthalmic diseases, and hematologic disorders.
These results also validate the safety and efficacy of our in-house GalNAc platform in humans. We are highly encouraged by these findings and looking forward to advancing subsequent clinical trials. We believe SGB-9768 will continue to demonstrate its potential as a 'best-in-class' C3-targeting siRNA drug."
About complement-mediated kidney diseases
The complement system is an important component of innate immunity, which regulates the adaptive immune response and plays an important role in the immunological and physiological functions in the human body, protecting the body from infections and removing dead cells and apoptotic material. However, dysregulation or overactivation of the complement system can induce inflammation and destroy self-tissues, causing immune damage, which is closely related to the occurrence and development of certain hematologic, ophthalmic, and kidney diseases. Chronic kidney disease (CKD) is a major public health concern worldwide, and in China, the prevalence of CKD is 10.8% among adults, meaning 1 in 10 adults has CKD. Complement is involved in the pathogenesis of many kidney diseases, such as IgAN, C3G, and IC-MPGN. Currently, there are limited options in the treatment of complement-mediated kidney diseases, with many complement-targeting drugs still in clinical research stages, indicating significant unmet clinical needs in this field. Complement inhibition holds promise as a new therapeutic target for complement-mediated kidney diseases. C3 is a critical component protein connecting upstream activation pathways to terminal pathways in the complement system. Inhibiting C3 activity has been validated to significantly suppress complement activation, making it a potent therapeutic target for these kidney diseases. Therefore, developing safe and effective siRNA drugs targeting C3 has important clinical application value for complement-mediated kidney diseases.
About SGB-9768
SGB-9768 is an siRNA drug candidate targeting the complement component 3 (C3) mRNA for the treatment of complement-mediated kidney diseases, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), Immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). SGB-9768 is developed using SanegeneBio's proprietary GalNAc platform, to reduce C3 through RNA interference, thereby inhibiting the complement pathway activity. Preclinical studies have demonstrated that SGB-9768 could be administered every 3 or 6 months and continuously reduce the C3 level, and has superior potency than benchmark compounds, with good safety and tolerability profile. SGB-9768 has the advantages of low dosing frequency and long-term efficacy, and could potentially become the leading siRNA drug targeting C3.
About SanegeneBio
SanegeneBio is an emerging RNAi-based company developing innovative RNA interference (RNAi) therapeutics driven by the cutting-edge delivery technology. Founded in 2021, SanegeneBio was led by a team of industry-leading experts and has operations in both the US and China. Since its incorporation, SanegeneBio has successfully established proprietary chemical modification platform, hepatic and extrahepatic delivery platforms, enabling tissue-specific delivery of a wide range of RNA therapeutics to efficiently knock down disease-causing genes. Our fast-growing RNAi portfolio covers a broad range of therapeutic areas including cardiovascular and metabolic diseases, immunology-related diseases, and nervous system diseases. Among them, our three RNAi drugs have entered into the clinical stage, and several pipelines are in progress simultaneously. SanegeneBio is committed to developing transformational RNAi medicines through striving for scientific innovation to address unmet medical needs worldwide and change the lives of patients and families. For further information, please visit: www.sanegenebio.com and engage with us on LinkedIn.
