Leads Biolabs Doses First Lupus Patient With LBL-047, a BDCA2/TACI Bifunctional Fusion Protein

Leads Biolabs has dosed the first patient with systemic lupus erythematosus (SLE) in Part B of its phase 1 trial of LBL-047, a first-in-class bifunctional fusion protein designed to block two drivers of lupus at once.¹ Outside Greater China, the molecule is being developed by Dianthus Therapeutics as DNTH212.¹˒²

“SLE is a heterogeneous autoimmune disease driven by complex interactions between innate and adaptive immunity,” said Charles Cai, MD, PhD, chief medical officer of Leads Biolabs.¹

How is LBL-047 designed?

LBL-047 combines a humanized antibody against BDCA2, a receptor found on plasmacytoid dendritic cells (pDCs), with an engineered domain of the receptor TACI.¹ The BDCA2 arm is designed to reduce production of type 1 interferon by pDCs, part of the innate immune response in lupus.¹ According to Dianthus, the antibody also carries an afucosylated Fc region that enhances antibody-dependent cellular cytotoxicity, which can deplete pDCs.²

The TACI portion acts as a decoy for BAFF and APRIL, two cytokines that drive B-cell activation, differentiation, and antibody production.¹ The molecule includes a YTE Fc mutation to extend its half-life, and the companies are targeting subcutaneous dosing every four weeks or less often.¹˒²

Each mechanism has been pursued separately. In a phase 2 trial published in the New England Journal of Medicine, Biogen’s anti-BDCA2 antibody litifilimab reduced active joint counts compared with placebo in patients with SLE, though most secondary endpoints did not support the finding.³ AstraZeneca’s anifrolumab (Saphnelo), which blocks the type 1 interferon receptor, is approved for SLE, and the European Commission cleared a subcutaneous formulation for self-administration in 2025, as BioPharm International® reported.⁴ In preclinical studies, Dianthus reported greater pDC depletion in vitro than litifilimab and greater immunoglobulin reductions in nonhuman primates than the BAFF/APRIL inhibitor povetacicept, though these were not head-to-head comparisons.²

What does the phase 1 trial involve?

The two-part trial (NCT07323173) is being conducted in China.¹˒⁵ Part A, in healthy volunteers at Shanghai Public Health Clinical Center, generated safety and pharmacokinetic data that supported moving into patients, though neither company has disclosed the results.¹ Dianthus has said it expects top-line healthy volunteer data in the second half of 2026.⁶

Part B will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with SLE.¹ The study is led by investigators at Renji Hospital, Shanghai Jiao Tong University School of Medicine.¹

Why target two pathways at once?

Combining innate and adaptive immune targets in a single molecule reflects a broader push toward multitarget approaches in autoimmune and inflammatory disease. In a BioPharm International interview at BIO 2026, Howard Berman, PhD, chief executive officer of ReAlta Life Sciences, described the rationale for that strategy in inflammatory disease. “Being able to hit all these targets at once is so critically and verifiably important to ameliorate the disease,” Berman said.

What is Dianthus’ role?

Dianthus licensed exclusive rights to the molecule outside Greater China in October 2025, paying $30 million upfront and near-term, with an additional $8 million due when a Dianthus-led phase 1 study begins.² Leads Biolabs is eligible for up to $962 million in development, regulatory, and sales milestones, plus tiered royalties.² FDA cleared a US Investigational New Drug application for DNTH212 in September 2025, and Dianthus has described it as “a first and potentially best-in-class” bifunctional BDCA2 and BAFF/APRIL inhibitor.²

Dianthus has selected Sjögren’s disease, SLE, and dermatomyositis as the first three priority indications for DNTH212.⁶ Leads Biolabs retains rights in Greater China, and Cai said the company will “work closely with Dianthus” on global development.¹

References

1. Leads Biolabs doses first patient with systemic lupus erythematosus in Phase I Part B trial of LBL-047, a first-in-class BDCA2/TACI bifunctional fusion protein. News release. Leads Biolabs. October 30, 2026. Accessed October 30, 2026.
2. Dianthus Therapeutics licensing of DNTH212 (BDCA2 and BAFF/APRIL) from Leads Biolabs. Investor presentation. Dianthus Therapeutics. October 16, 2025. Accessed October 30, 2026.
3. Furie RA, van Vollenhoven RF, Kalunian K, et al; LILAC Trial Investigators. Trial of anti-BDCA2 antibody litifilimab for systemic lupus erythematosus. N Engl J Med. 2022;387(10):894-904. doi:10.1056/NEJMoa2118025
4. Saphnelo approved in the EU for subcutaneous self-administration as a new pre-filled pen for systemic lupus erythematosus. News release. AstraZeneca. December 16, 2025. Accessed October 30, 2026.
5. A study to assess the safety and PK/PD of LBL-047 in healthy adults and patients with systemic lupus erythematosus. ClinicalTrials.gov. Accessed October 30, 2026.
6. Dianthus Therapeutics highlights recent business achievements and reports Q1 2026 financial results. News release. Dianthus Therapeutics. May 5, 2026. Accessed October 30, 2026.