China NMPA Clears Phase 2 Trial of First-in-Class Sialidase Enzyme Therapy for Autoimmune Kidney Disease
核心洞察
China's NMPA has approved a Phase 2 clinical trial for E-602 (HLX79), a first-in-class human sialidase enzyme therapeutic, in combination with rituximab for treating active glomerulonephritis (搜索) including lupus nephritis (搜索).
The therapy uses glyco-immunology to enhance B cell depletion by enzymatically degrading sialoglycans (搜索) that protect pathogenic memory B cells (搜索) from antibody-mediated elimination.
Preclinical studies demonstrate improved outcomes versus rituximab alone without the cytokine release syndrome risks associated with CAR-T therapies, addressing China's 3.5 million ESRD patients.
China's National Medical Products Administration (NMPA) has cleared a Phase 2 clinical trial for E-602 (HLX79), a first-in-class human sialidase enzyme therapeutic, in combination with rituximab for patients with active glomerulonephritis (搜索), including lupus nephritis (搜索). The approval, announced by Shanghai Henlius Biotech (搜索) and Palleon Pharmaceuticals (搜索), represents the first clinical trial of Palleon's glyco-immunology platform in autoimmune diseases (搜索).
Novel Glyco-Immunology Approach
E-602 is designed to address a critical limitation in current B cell-targeted therapies by enhancing the depletion of autoreactive memory B cells (搜索) and reducing dysfunctional M2 macrophages. The therapy works by enzymatically degrading sialoglycans (搜索)—immunosuppressive cell surface sugars that protect pathogenic memory B cells from depletion by B cell-targeted antibodies.
"Glyco-immunology provides an entirely new approach to treating autoimmune disorders," said Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon. "E-602 (HLX79) has the potential to pair improved patient outcomes with optimal accessibility, including delivery in community outpatient settings."
The dual mechanism targets two key immune cell types involved in autoimmunity: autoreactive memory B cells (搜索) and dysfunctional M2 macrophages that cause tissue damage and scarring after autoimmune flares. This approach is expected to reduce the severity of autoimmune flares and improve treatment response.
Addressing Significant Unmet Need
China accounts for nearly 30% of global end-stage renal disease (搜索) (ESRD) cases, with approximately 3.5 million patients facing high disease severity, complications, and substantial economic burden. Glomerulonephritis (搜索) represents the leading cause of ESRD in China, encompassing both primary forms like membranous nephropathy (搜索) and focal segmental glomerulosclerosis (搜索), and secondary forms including lupus nephritis (搜索) and ANCA-associated vasculitis.
While B cell depletion with rituximab has been approved in multiple markets and is recognized by Chinese nephrology expert consensus for treating glomerulonephritis (搜索), many patients demonstrate inadequate response to these therapies. The pathogenic subset of activated memory B cells (搜索) associated with disease progression often remains resistant to antibody-mediated depletion.
Preclinical and Safety Data
Preclinical studies of E-602 in combination with rituximab demonstrate enhanced B cell depletion versus rituximab alone, crucially without the risk of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) that have been associated with CAR-T and T cell engager therapies for eliminating autoreactive B cells (搜索).
E-602 demonstrated a favorable safety profile with no dose-limiting toxicities in a completed Phase 1 clinical trial, making it suitable for outpatient community settings. This safety profile represents a significant advantage over more intensive cellular therapies currently being explored for autoimmune diseases (搜索).
Strategic Collaboration
The Phase 2 trial will be conducted under a collaboration between Palleon and Henlius announced in December 2024. The study will evaluate E-602 in combination with Henlius' HANLIKANG (搜索), a rituximab biosimilar that was approved in 2022 for rheumatoid arthritis (搜索) and remains the only rituximab approved for an autoimmune indication in China.
The combination therapy is expected to benefit patients with active glomerulonephritis (搜索) by providing enhanced therapeutic efficacy while maintaining the safety profile suitable for community-based treatment. This represents the most advanced trial of E-602 to date and could establish a new category of medicines for challenging autoimmune diseases (搜索).