Jade Biosciences has unveiled JADE201, an investigational half-life extended, afucosylated monoclonal antibody targeting the B-cell activating factor receptor (BAFF-R) designed to address limitations of current B cell-directed therapies for autoimmune diseases. The clinical-stage biotechnology company announced the development on October 7, 2025, positioning JADE201 as a potentially best-in-class therapy that combines validated mechanisms with enhanced pharmacological properties.
Addressing Current Treatment Limitations
Current B-cell depleting therapies face significant challenges, as they may spare important pathogenic B cell populations and risk resistance and relapse due to elevated BAFF signaling that drives B cell repopulation and autoreactivity. JADE201 was engineered with high binding affinity to BAFF-R, supporting robust receptor engagement across multiple B cell subsets to address these limitations.
"JADE201 reflects the progress we are making to build a complementary portfolio of therapies that modulate B-cell biology," said Tom Frohlich, Chief Executive Officer of Jade. "JADE201 combines a validated mechanism of action with half-life extension designed to enable potent activity with more patient-friendly, infrequent dosing as we work to advance new standards of care for autoimmune diseases."
Dual Mechanism of Action and Enhanced Properties
JADE201 incorporates afucosylation to enhance antibody-dependent cellular toxicity and a clinically validated Fc mutation to increase neonatal Fc receptor binding, with the goal of extending systemic exposure while preserving activity. The antibody is designed with a dual mechanism of action that combines enhanced B cell depletion via antibody-dependent cellular toxicity and blockade of BAFF-R mediated survival and activation signals.
Andrew King, Chief Scientific Officer and Head of R&D at Jade, explained, "With JADE201, we are building directly on the clinical validation of targeting BAFF-R. Its dual mechanism of action combines enhanced B cell depletion via antibody-dependent cellular toxicity and blockade of BAFF-R mediated survival and activation signals. JADE201 is designed to deliver deeper, more durable B-cell depletion with less frequent subcutaneous dosing, potentially providing a differentiated therapy across multiple autoimmune diseases."
Building on Clinical Validation
The clinical proof-of-concept for BAFF-R inhibition has been established by ianalumab, which has shown activity across multiple autoimmune indications, including in multiple recent positive Phase 3 trials. JADE201 builds on the desirable pharmacological benefits of ianalumab while addressing its relatively short human half-life by adding half-life extension technology to extend drug exposure, with the potential to enable less frequent subcutaneous dosing and enhance efficacy.
Preclinical Results Demonstrate Enhanced Performance
In non-human primate studies, JADE201 achieved dose-dependent BAFF receptor occupancy, sustained B cell depletion after a single subcutaneous dose, and demonstrated approximately a two-fold increase in half-life compared with ianalumab. This extended exposure is designed to improve durability and convenience while preserving potency, with the goal of reducing treatment burden and potentially enhancing efficacy.
Clinical Development Timeline
Jade expects to initiate a first-in-human study evaluating JADE201 in patients with rheumatoid arthritis in the first half of 2026. The randomized, placebo-controlled, single ascending dose trial will assess safety, tolerability, pharmacokinetics, and pharmacodynamics, with biomarker-rich endpoints including BAFF-R occupancy, soluble BAFF levels, and B cell subpopulation profiling.
Expanding Autoimmune Portfolio
JADE201 bolsters Jade's portfolio of autoimmune disease therapies, which includes JADE101, a potentially best-in-class anti-APRIL monoclonal antibody currently being evaluated in a Phase 1 clinical trial for the treatment of immunoglobulin A nephropathy. JADE101 is a fully human monoclonal antibody that selectively blocks APRIL with ultra-high binding affinity and is engineered for half-life extension, with preclinical studies demonstrating a serum half-life of approximately 27 days in non-human primates.
The company's pipeline also includes JADE-003, an undisclosed antibody discovery program currently in preclinical development. Jade was launched based on assets licensed from Paragon Therapeutics, an antibody discovery engine founded by Fairmount, and maintains a focus on developing best-in-class therapies that address critical unmet needs in autoimmune diseases.
