FDA Clears IND for Alebund's First-in-Class IgA Protease AP308 in IgA Nephropathy
核心洞察
Alebund Pharmaceuticals (搜索) received US FDA clearance of its IND application for AP308, a first-in-class engineered recombinant IgA protease (搜索) for IgA nephropathy (搜索).
AP308 is designed to directly cleave IgA1, galactose-deficient IgA1 (搜索), polymeric IgA and IgA immune complexes, including deposits already present in the glomeruli.
Preclinical data published in Kidney International showed once-weekly subcutaneous dosing reduced circulating human IgA and IgA immune complexes by roughly 80% in a humanized mouse model.
Alebund Pharmaceuticals (搜索) (Jiangsu) Limited (HKEX: 09637) has received clearance from the US Food and Drug Administration (搜索) for its Investigational New Drug application for AP308, a first-in-class engineered recombinant IgA protease (搜索) being developed for IgA nephropathy (搜索) (IgAN). The company said it plans to initiate a first-in-human clinical trial in the near term, marking the transition of the candidate from preclinical research into clinical development.
A Mechanistically Distinct Approach
AP308 is designed to act differently from current and emerging IgAN therapies. Rather than suppressing IgA production or blocking downstream inflammatory pathways, the molecule directly cleaves IgA1, galactose-deficient IgA1 (搜索) (Gd-IgA1), polymeric IgA and IgA immune complexes, and clears IgA immune complexes and complement C3 already deposited in the glomeruli. In preclinical studies, the enzyme acted within minutes and did not affect other immunoglobulins such as IgG and IgM.
The drug is based on an IgA protease (搜索) derived from Thomasclavelia ramosa, a human commensal bacterium. Alebund engineered the enzyme using its proprietary Long-Acting Protease Engineering Platform, which the company says extends circulating half-life, reduces renal clearance and lowers immunogenicity while preserving potent cleavage activity against IgA1, enabling long-acting, low-frequency dosing. Alebund holds global rights to develop, manufacture and commercialize AP308.
The company began working with Peking University First Hospital (PUFH) in January 2022 to develop IgA proteases as potential IgAN treatments and entered into a license agreement with PUFH, subsequently nominating AP308 as a drug candidate.
Preclinical Data Published in Kidney International
Preclinical results supporting clinical advancement were published in May 2026 in Kidney International, the official journal of the International Society of Nephrology. In a humanized mouse model of IgAN, once-weekly subcutaneous dosing of AP308 over an eight-week treatment period reduced circulating human IgA and IgA immune complexes by approximately 80% relative to controls. At the end of treatment, histological examination confirmed that glomerular IgA deposits were almost completely cleared, proteinuria decreased significantly and kidney pathology improved markedly.
In a separate paired pre- and post-treatment design, a single dose completely cleared pre-existing chronic glomerular IgA and complement C3 deposits within seven days. Repeated dosing produced no signals of liver or kidney toxicity and no significant increase in anti-drug antibody titers.
Unmet Need in IgA Nephropathy
IgAN is the most common primary glomerulonephritis worldwide. It is characterized by the deposition of IgA-containing immune complexes in the glomeruli, leading to inflammation and progressive kidney damage with a poor long-term prognosis. Long-term cohort studies in China and the United Kingdom show that, under current treatment strategies, median kidney survival is approximately 11 to 12 years, and most patients progress to end-stage renal disease within 10 to 15 years of diagnosis, with approximately 60% of patients in the Chinese cohort reaching end-stage renal disease within 15 years.
According to China Insights Consultancy, there were approximately 9.5 million IgAN patients globally in 2025, including approximately 5.1 million in China — more than half of the global total and the largest IgAN patient population in the world.
The current IgAN treatment landscape includes therapies targeting IgA production, endothelin and angiotensin signaling, and complement-mediated inflammation. Alebund positions AP308 as differentiated by its proposed ability to remove already-deposited immune complexes from the kidney, a mechanism the company acknowledges has yet to be validated clinically. Existing and emerging therapies mainly target IgA production or downstream inflammation, leaving strategies to directly clear IgA immune complexes already deposited in the kidney to be further explored.
Alebund is a renal-focused biopharmaceutical company with an integrated platform spanning R&D, manufacturing and commercialization. Its portfolio comprises seven investigational drug candidates and one commercialized product, Mircera.