Jade Biosciences Presents JADE101 Preclinical Data at the 62nd European Renal Association Congress Demonstrating Potential for Best-in-Class Profile in IgA Nephropathy

Rhea-AI Summary

Jade Biosciences (NASDAQ: JBIO) presented promising preclinical data for JADE101, its anti-APRIL monoclonal antibody for IgA nephropathy treatment, at the 62nd ERA Congress. The data revealed JADE101's superior profile with femtomolar APRIL binding affinity (50 fM), 750-fold higher than competitor sibeprenlimab. In non-human primates, JADE101 demonstrated a 27-day half-life, nearly 4x longer than sibeprenlimab, with sustained IgA suppression lasting over 100 days after a single dose. The drug showed high subcutaneous bioavailability and was designed to avoid immune complex formation risks. At just 4 mg/kg, JADE101 achieved better results than 30 mg/kg of sibeprenlimab. The company plans to initiate human trials in H2 2025, with interim data expected in H1 2026.

Positive

• Ultra-high APRIL binding affinity (50 fM), 750-fold higher than competitor sibeprenlimab
• Extended 27-day half-life in non-human primates, 4x longer than competitor
• Sustained IgA suppression for over 100 days after single dose
• Superior efficacy at lower doses (4 mg/kg vs competitor's 30 mg/kg)
• High subcutaneous bioavailability supporting convenient dosing every 8 weeks or longer
• Designed to reduce risks associated with immune complex formation

Negative

• First-in-human trials yet to begin, with data not expected until first half 2026
• Clinical efficacy and safety in humans remains unproven
• Potential competition from sibeprenlimab which is in later development stages

Insights

Biotechnology Research Scientist

JADE101 shows superior preclinical profile for IgA nephropathy with ultra-high binding affinity and extended dosing potential.

Jade Biosciences' presentation at the ERA Congress reveals JADE101 as a potentially significant advancement for IgA nephropathy (IgAN) treatment. The preclinical data demonstrates several compelling advantages over existing anti-APRIL approaches.

The molecular design incorporates a YTE-modified IgG1 backbone that delivers remarkable femtomolar binding affinity (approximately 50 fM) – over 750-fold higher than the comparator sibeprenlimab. This ultra-high affinity enables complete APRIL suppression at low plasma concentrations, potentially maximizing efficacy.

Pharmacokinetic data in non-human primates shows JADE101 maintains an approximately 27-day half-life, nearly four times longer than sibeprenlimab at equivalent dosing. Most impressive is that JADE101 at just 4 mg/kg achieved deeper and more durable IgA suppression than sibeprenlimab at 30 mg/kg – demonstrating potential dose efficiency.

The subcutaneous administration profile is particularly noteworthy, with high bioavailability and linear half-life exceeding 30 days supporting potential dosing intervals of 8+ weeks. For a chronic condition like IgAN that requires lifelong treatment, this could significantly improve treatment adherence and quality of life.

JADE101's novel epitope binding approach may mitigate risks associated with high molecular weight immune complex formation seen with first-generation anti-APRIL antibodies, potentially offering more consistent pharmacokinetics and improved safety profile.

The transition to first-in-human trials in H2 2025 with interim biomarker data expected H1 2026 represents a critical development milestone that will validate whether these impressive preclinical characteristics translate to human subjects.

Preclinical data highlighted JADE101’s femtomolar APRIL binding affinity, extended non-human primate half-life of approximately 27 days, and sustained IgA suppression

In non-human primates, JADE101 showed a differentiated pharmacokinetic and pharmacodynamic profile with deep and sustained IgA reductions and the potential to support convenient subcutaneous dosing every eight weeks or longer

First-in-human trial expected to begin second half 2025; biomarker-rich interim data in healthy volunteers expected first-half 2026 to inform patient dose and schedule

Company to host conference call and webcast today, June 9, 2025, at 8:00 a.m. ET

SAN FRANCISCO and VANCOUVER, British Columbia, June 09, 2025 (GLOBE NEWSWIRE) -- Jade Biosciences, Inc. (“Jade”) (Nasdaq: JBIO), 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.
  
  
• Favorable subcutaneous profile in NHPs
  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.
  
  
• Designed to reduce risk of high molecular weight immune complex formation
  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.

Conference Call and Webcast

Jade Biosciences will host a conference call and webcast today, Monday, June 9, 2025, at 8:00 a.m. ET to review the JADE101 data presented at ERA 2025.

Investors and the public are invited to join the live webcast by registering on the “Events and Presentations” page of JadeBiosciences.com. To join the conference call, participants must register here. Upon registering, dial-in details and a unique PIN will be provided. A replay of the webcast will be available shortly after the call concludes.

About IgA nephropathy (IgAN)

IgAN is a chronic autoimmune kidney disease that affects approximately 169,000 people in the U.S. and is most often diagnosed in young adults. The disease is characterized by the deposition of pathogenic IgA-containing immune complexes in the kidneys. These deposits can lead to increased protein in the urine, also known as proteinuria, declining kidney function, and potentially end-stage kidney disease requiring dialysis or a transplant. IgAN often requires lifelong treatment to preserve kidney function and prevent progression to kidney failure.

About JADE101

JADE101 is an anti-APRIL monoclonal antibody being developed for the treatment of IgAN. By targeting APRIL, a protein involved in the overproduction of IgA, JADE101 aims to reduce the levels of disease-driving IgA, decrease proteinuria, and preserve kidney function. Engineered with half-life extension technology, JADE101 is designed for dosing at intervals of at least eight weeks, offering the potential for durable clinical activity and improved patient convenience, particularly important for a condition often diagnosed in young adulthood and potentially requiring life-long treatment.

About Jade Biosciences, Inc.

Jade Biosciences is focused on developing best-in-class therapies to address critical unmet needs in autoimmune diseases. Its lead candidate, JADE101, targets the cytokine APRIL for the treatment of immunoglobulin A nephropathy, with initiation of a first-in-human clinical trial expected in the second half of 2025. Jade’s pipeline also includes a second development candidate, JADE201, and an undisclosed antibody discovery program, JADE-003, both currently in preclinical development. Jade was launched based on assets licensed from Paragon Therapeutics, an antibody discovery engine founded by Fairmount. For more information, visit JadeBiosciences.com and follow the Company on LinkedIn.

Forward-Looking Statements

Certain statements in this communication, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the "safe harbor" provisions under the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements relating to Jade’s expectations, hopes, beliefs, intentions or strategies regarding the future of its pipeline and business including, without limitation, Jade’s ability to achieve the expected benefits or opportunities with respect to JADE101, JADE201 and the JADE-003 program, including without limitation the expected timelines for JADE101 entering the clinic and interim data from such trial, the potential of Jade’s product candidates to become best-in-class therapies and their potential therapeutic uses, efficacy, dosing, safety and market opportunities. The words "opportunity," "potential," "milestones," "pipeline," "can," "goal," "strategy," "target," "anticipate," "achieve," "believe," "contemplate," "continue," "could," "estimate," "expect," "intends," "may," "plan," "possible," "project," "should," "will," "would" and similar expressions (including the negatives of these terms or variations of them) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs concerning future developments and their potential effects. There can be no assurance that future developments affecting Jade will be those that have been anticipated. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Jade's control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, the risks that the planned trial of JADE101 and any future clinical trials may be delayed or may not demonstrate safety and/or efficacy; Jade may experience unanticipated costs, difficulties or delays in the product development process; Jade’s product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; risks associated with Jade’s dependence on third-party vendors for the development, manufacture and supply of JADE101; and the other risks, uncertainties and factors more fully described in Jade’s most recent filings with the Securities and Exchange Commission (including the definitive proxy statement/prospectus filed on Form S-4, most recently amended on March 24, 2025 and declared effective on March 25, 2025). Should one or more of these risks or uncertainties materialize, or should any of Jade's assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. You should not place undue reliance on forward-looking statements in this communication, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Jade does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements. This communication does not purport to summarize all of the conditions, risks and other attributes of an investment in Jade.

Jade Biosciences Media & Investor Contacts

Priyanka Shah
Email: Media@JadeBiosciences.com
Email: IR@JadeBiosciences.com
Phone: 908-447-6134

FAQ

What are the key advantages of JADE101 over sibeprenlimab for IgA nephropathy treatment?

JADE101 shows 750-fold higher binding affinity, 4x longer half-life, and superior efficacy at lower doses (4 mg/kg vs 30 mg/kg) compared to sibeprenlimab, with potential for 8-week or longer dosing intervals.

When will Jade Biosciences (JBIO) begin human trials for JADE101?

Jade Biosciences plans to initiate first-in-human trials for JADE101 in healthy volunteers during the second half of 2025.

What were the main findings from JADE101's preclinical studies presented at ERA 2025?

JADE101 demonstrated femtomolar APRIL binding affinity, 27-day half-life in non-human primates, sustained IgA suppression for over 100 days, and high subcutaneous bioavailability.

How does JADE101's dosing schedule compare to existing IgA nephropathy treatments?

JADE101's preclinical data suggests potential for convenient subcutaneous dosing every eight weeks or longer, supported by its extended half-life and sustained therapeutic effects.

What is the significance of JADE101's reduced immune complex formation?

JADE101's design to avoid immune complex formation may reduce risks of immunogenicity, tissue deposition, and accelerated drug clearance, potentially supporting more consistent and sustained therapeutic exposure.