Leads Biolabs and Dianthus Therapeutics Initiate Phase 1 Trial of Novel Bifunctional Autoimmune Therapy LBL-047
核心洞察
Leads Biolabs (搜索) and Dianthus Therapeutics have successfully dosed the first subject in a Phase 1 trial of LBL-047 (DNTH212 (搜索)), a bifunctional fusion protein targeting both innate and adaptive immune pathways in autoimmune diseases (搜索).
The investigational therapy simultaneously targets plasmacytoid dendritic cells (搜索) to reduce Type 1 interferon production while inhibiting BAFF (搜索)/APRIL (搜索) pathways to suppress B-cell function, potentially addressing limitations of single-target therapies.
The two-part Phase 1 trial will evaluate safety, tolerability, and pharmacokinetics in healthy volunteers and systemic lupus erythematosus (搜索) patients, with top-line results expected in the second half of 2026.
Leads Biolabs (搜索) and Dianthus Therapeutics have successfully initiated dosing in a Phase 1 clinical trial of LBL-047 (DNTH212 (搜索)), a potentially first- and best-in-class bifunctional fusion protein designed to target multiple pathways in autoimmune diseases (搜索). The companies announced that the first subject has been dosed in the study evaluating this novel therapeutic approach for systemic lupus erythematosus (搜索) and other autoimmune conditions.
Dual-Pathway Targeting Strategy
LBL-047 represents a differentiated approach to autoimmune disease treatment by simultaneously targeting both innate and adaptive immune systems. The bifunctional fusion protein is composed of a humanized anti-blood dendritic cell antigen 2 (BDCA2 (搜索)) antibody and an engineered transmembrane activator and CAML interactor (TACI (搜索)) ectodomain.
The therapy is designed to selectively deplete plasmacytoid dendritic cells (搜索) (pDCs) to reduce type 1 interferon production, while simultaneously inhibiting B-cell activating factor (BAFF (搜索)) and a proliferation-inducing ligand (APRIL (搜索)) signaling pathways to suppress B-cell activation, differentiation, and antibody production. This dual mechanism targets two clinically validated pathways known to drive autoimmune disease pathogenesis.
"By simultaneously targeting multiple pathways, LBL-047 is designed to address the limitations of single-target therapies," said Dr. Charles Cai, Chief Medical Officer of Leads Biolabs (搜索). "We look forward to advancing this program in collaboration with Dianthus Therapeutics to deliver potentially transformative options for patients worldwide."
Phase 1 Trial Design and Timeline
The ongoing Phase 1 study is a two-part, double-blind, randomized, placebo-controlled, dose-escalation trial using single ascending doses. Part A evaluates the therapy in healthy volunteers under the leadership of Professor Meng Xianmin at Shanghai Public Health Clinical Center, while Part B focuses on patients with systemic lupus erythematosus (搜索), led by Professors Ye Shuang and Chen Sheng at Renji Hospital, Shanghai Jiaotong University School of Medicine.
The trial is designed to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profile of LBL-047. Top-line results in healthy volunteers are anticipated in the second half of 2026, with Dianthus expected to provide an update on indication prioritization in the first half of 2026.
Optimized for Patient Convenience
LBL-047 has been optimized with Fc engineering to extend its half-life, enabling a patient-friendly subcutaneous self-administration regimen with dosing frequency of every four weeks (Q4W) or less. This optimization supports its potential as a first-line biologic therapy across multiple autoimmune indications.
"Initiating this Phase 1 study is the first step to realizing the much anticipated by physicians outcome of targeting multiple pertinent dysfunctional pathways in several autoimmune indications," said Dr. Simrat Randhawa, Head of Research & Development at Dianthus Therapeutics.
Strategic Partnership and Development
The development of LBL-047 is supported by a significant partnership between the two companies. On October 16, 2025, Leads Biolabs (搜索) entered into an exclusive global partnership with Dianthus, with total potential deal value reaching up to $1 billion. Under this agreement, Dianthus licensed exclusive global rights from Leads Biolabs to research, develop, manufacture, and commercialize LBL-047 outside Greater China, where it is known as DNTH212 (搜索).
This collaboration aims to jointly advance the global development of the therapy to maximize its clinical and commercial potential across multiple autoimmune indications. The complementary and differentiated approach of targeting both innate and adaptive immune systems has the potential to address multiple autoimmune indications with improved outcomes compared to existing single-target therapies.