Jade Biosciences presents JADE101 preclinical data at ERA Congress

Jade Biosciences (JBIO) announced a detailed preclinical characterization of JADE101, its anti-A Proliferation-Inducing Ligand monoclonal antibody, in development for IgA nephropathy, a chronic autoimmune kidney disease. The findings, presented during an oral session at the 62nd European Renal Association Congress, support advancement of JADE101 into a planned healthy volunteer study in the second half of 2025. Jade’s presentation at ERA focused on a comprehensive preclinical characterization of JADE101, a fully human monoclonal antibody targeting APRIL, designed to address key limitations of earlier molecules in this class. JADE101 incorporates a YTE-modified IgG1 backbone and was engineered to improve target affinity, extend pharmacokinetic exposure, and reduce risks associated with immune complex formation and rapid clearance. The molecular design of JADE101 prolonged systemic exposure that delivers sustained target engagement, with a goal of supporting clinical dosing intervals of eight weeks or potentially longer. JADE101 was compared with sibeprenlimab, an investigational late-stage anti-APRIL monoclonal antibody, manufactured from publicly available sequences. A YTE-engineered version of sibeprenlimab was also tested to isolate the impact of Fc modification on pharmacokinetic profiles in non-human primates. Key findings included: JADE101 binds APRIL with femtomolar affinity, over 750-fold higher affinity than sibeprenlimab. This higher binding affinity has the potential to enable complete suppression of APRIL at low plasma concentrations of JADE101 to deliver the full efficacy available to the anti-APRIL mechanism and further support an extended dosing interval. JADE101 demonstrated potent blockade of APRIL binding and signaling through its receptors in in vitro assays, including assays designed to model mechanistic aspects of the therapeutic benefit of APRIL inhibition in IgAN. In competitive binding assays, JADE101 fully inhibited APRIL binding to its receptors BCMA and TACI with IC50 values of 1.9 nM and 1.03 nM, respectively. In cell-based reporter assays, JADE101 blocked APRIL-induced signaling through BCMA and TACI. JADE101 also potently reduced human plasma cell proliferation and IgA secretion in vitro. In NHPs, a single 30 mg/kg intravenous dose of JADE101 demonstrated an approximately 27-day half-life, nearly 4 times longer than sibeprenlimab at the same dose, and maintained linear clearance down to approximately 2 microgram/mL, well below the approximately 40 microgram/mL target-mediated drug disposition threshold observed for sibeprenlimab. This pharmacokinetic profile translated into sustained IgA suppression for more than 100 days after a single 30 mg/kg dose in NHPs. Notably, JADE101 dosed at just 4 mg/kg achieved deeper and more durable IgA reductions in NHPs than both sibeprenlimab and YTE-modified sibeprenlimab dosed at 30 mg/kg. Following a single 100 mg/kg subcutaneous dose, JADE101 exhibited high bioavailability and a linear half-life exceeding 30 days in NHPs, supporting the potential for convenient, infrequent subcutaneous dosing in clinical settings. JADE101 binds a novel epitope on trimeric APRIL and was specifically selected to avoid the formation of high molecular weight immune complexes, that can occur with the first-generation anti-APRIL monoclonal antibodies. Immune complexes have potential to be associated with an increased risk of immunogenicity and tissue deposition, and to result in accelerated drug clearance. By avoiding their formation, JADE101 may mitigate these risks, supporting more consistent pharmacokinetics and sustained exposure over time. Jade plans to initiate a study of JADE101 in healthy volunteers in the second half of 2025. The study will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and suppression of key biomarkers including APRIL and IgA. Interim data are expected in the first half of 2026 and are anticipated to guide dose and dose interval selection for future JADE101 studies in patients with IgAN.