Jade Biosciences Presents JADE101
Jade Biosciences Presents JADE101 Preclinical Data at the 62nd European Renal Association Congress Demonstrating Potential for Best-in-Class Profile in IgA Nephropathy
SAN FRANCISCO and VANCOUVER, British Columbia -- Jade Biosciences, Inc., a biotechnology company focused on developing best-in-class therapies for autoimmune diseases, today announced a detailed preclinical characterization of JADE101, its anti-A Proliferation-Inducing Ligand (APRIL) monoclonal antibody, in development for IgA nephropathy (IgAN), a chronic autoimmune kidney disease. The findings, presented during an oral session at the 62nd European Renal Association (ERA) Congress, support advancement of JADE101 into a planned healthy volunteer study in the second half of 2025.
“IgA nephropathy often begins in young adulthood and typically requires lifelong treatment, yet current treatment options have limitations in efficacy and ease of use,” said Andrew King, BVMS, Ph.D., Chief Scientific Officer and Head of R&D at Jade Biosciences. “Jade’s preclinical data presented at ERA demonstrate JADE101’s potential to be a best-in-class disease-modifying therapy. JADE101 has the potential to fully capture the efficacy available to the anti-APRIL mechanism with convenient, infrequent dosing. We believe this profile could translate into meaningful long-term benefit for patients, and we look forward to advancing this promising candidate into the clinic later this year.”
Summary of Jade Biosciences’ ERA 2025 Presentation
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 (NHPs).
Key findings included:
Ultra-high APRIL binding affinity
JADE101 binds APRIL with femtomolar affinity (approximately 50 fM), 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.
Potent inhibition of APRIL signaling through BCMA and TACI
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 (IC50 = 5.97 nM) and TACI (IC50 = 0.22 nM). JADE101 also potently reduced human plasma cell proliferation and IgA secretion in vitro.
Extended pharmacokinetics and deep, sustained IgA suppression in NHPs
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 µg/mL, well below the approximately 40 µg/mL target-mediated drug disposition (TMDD) 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 (7.5-fold lower) achieved deeper and more durable IgA reductions in NHPs than both sibeprenlimab and YTE-modified sibeprenlimab dosed at 30 mg/kg.
