From September 17 to 20, 2025, the 18th International IgA Nephropathy Symposium (IIgANN 2025) was held in Prague, Czech Republic. At the conference, Frontier Biotech presented, via an oral presentation, the first set of preclinical data of its self-developed, potentially first-in-class dual-target siRNA drug candidate FB7011. This drug simultaneously targets MASP-2, a key protein in the lectin pathway and CFB, a key protein in the alternative pathway of the complement system, precisely intervening in the abnormal activation of the complement system to block the pathogenesis of IgA nephropathy. 

In cynomolgus monkeys, a single subcutaneous administration of FB7011 (6 mg/kg) resulted in strong and sustained inhibition of both MASP-2 and CFB target proteins, with maximum inhibition efficiencies exceeding 95% for both targets. The inhibitory effect lasted for over 12 weeks, suggesting that in humans it could support dosing every 4-6 months. In a cynomolgus monkey IgA nephropathy model, a single subcutaneous dose of FB7011 significantly improved disease progression-related indicators (uTP, uPCR, and eGFR), demonstrating therapeutic effects. Additionally, FB7011 showed low off-target risk and immunotoxicity, exhibiting good safety in animal experiments. The presentation on FB7011 attracted attention from clinical experts and researchers. Its novel mechanism of action is expected to potentially provide IgA nephropathy patients with a new, effective and safe treatment option while significantly improving adherence. 

Another potential first-in-class siRNA drug candidate, FB7013, which targets MASP-2, also demonstrated excellent preclinical data. In healthy monkeys, a single subcutaneous dose of FB7013 led to a sustained reduction of the target protein for 16 weeks, suggesting a clinical dosing regimen of one injection every 4-6 months. In a cynomolgus monkey IgA nephropathy model, administration for 8 weeks effectively suppressed disease progression. FB7013 showed promising therapeutic potential, including improving the key IgA nephropathy indicators such as uPCR, and significantly reducing the renal pathological impairment.

Both FB7011 and FB7013 feature novel mechanisms of action, with no similar siRNA drugs approved or in clinical trials globally. Their significant differentiated advantages are expected to improve the treatment of IgA nephropathy and potentially be combined with drugs of different mechanisms to treat a broader patient population. 

Professor Zhang Hong, Director of the Nephrology Department at Peking University First Hospital, member of the International IgA Nephropathy Network commented: "The preclinical data of Frontier Biotech’s two drug candidates in the IgA nephropathy treatment field are highly noteworthy. First, FB7013 is the first siRNA drug targeting MASP-2, a key factor in the lectin pathway, and has the potential to become a novel mechanism drug for complement-mediated diseases like IgA nephropathy. Efficacy indicators showed 'positive signals,' including reduced 24-hour urine protein, improved eGFR, decreased glomerular IgA deposition, and simultaneously improved mesangial proliferation scores in the cynomolgus monkey model. If these results can be replicated in humans, the potential for dosing once every six months could redefine the current daily/weekly' treatment paradigm. Of course, this report is based on rodent and primate data, and the real test will be the clinical data." 

"Second, the dual-target drug FB7011 simultaneously targets both the lectin and alternative pathways—a design not seen in existing small molecules or monoclonal antibodies. Since complement activation in IgA nephropathy often involves both pathways, FB7011’s 'dual-pathway interception' mechanism is innovative. Overall, FB7013 and FB7011 provide a completely new intervention strategy for IgA nephropathy. If they successfully pass early clinical trials and demonstrate histological benefits in large samples, they could become the next benchmark for complement-targeted therapy in IgA nephropathy. We look forward to further clinical studies translating this 'laboratory concept' into 'patient benefits'." 

IgA nephropathy is the most common primary glomerulonephritis globally, with a large patient base and high risk of disease progression. According to statistics, the global patient population is expected to exceed 10.2 million by 2030, with approximately 4.59 million adult patients in China and over 100,000 new cases annually. Notably, 80% of patients are aged 20-59. More critically, over half of the patients may progress to end-stage renal disease (ESRD) within 20 years of diagnosis, requiring dialysis or kidney transplantation to sustain life. The first-year cost of dialysis ranges from 120,000 to 200,000 RMB, with subsequent annual costs of 90,000 to 160,000 RMB. In China, annual medical insurance expenditures for dialysis patients reach 38.6 to 39.4 billion RMB, placing a heavy burden on patients’ families and the healthcare system. 

Currently, treatment options for IgA nephropathy are limited, creating an urgent need for safe, effective, and convenient targeted therapies. The vast market potential remains untapped. Frontier Biotech will accelerate the clinical development of its pipeline, striving to develop the world’s first dual-target siRNA drug for IgA nephropathy and provide a breakthrough treatment for this "silent epidemic."