NANJING, China I June 17, 2024 I At the recent European League Against Rheumatism (EULAR) Congress in Vienna, Austria, Nanjing Leads Biolabs Co., Ltd. (Leads Biolabs) delivered an oral presentation on its highly innovative therapeutic candidate LBL-047. LBL-047 is a first-in-class, long-acting TACI/BDCA2 bispecific antibody fusion protein. LBL-047 is composed of a Transmembrane Activator and a Calcium Modulator and Cyclophilin Ligand Interactor (TACI) domain fused to an antibody targeting Blood Dendritic Cell Antigen 2 (BDCA2). The bispecific antibody is further modified with the YTE mutation on the Fc region to prolong the half-life in circulation, thereby, enabling less frequent dosing, and improved patient compliance.

LBL-047 has demonstrated excellent activity and pharmacokinetic properties in multiple preclinical experiments.

  • Significantly inhibit INF-α release
  • Robust depletion of pDCs in vitro and in vivo
  • Superior inhibition of B cell and plasma cell function in vitro and in vivo compared to marketed TACI fusion protein
  • Significantly alleviated clinical symptoms and inhibited B cell and plasma cell function in EAE mouse model (MS model)
  • Excellent PK profile and markedly reduced IgM, IgA, IgG in cynomolgus monkey for up to six weeks

These results indicate that LBL-047 can simultaneously inhibit B cell function and deplete interferon-secreting pDCs, thereby attenuating autoimmune activity. This innovative research offers new possibilities for treating a wide range of autoimmune related diseases, including Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Lupus Nephritis (LN), Sjogren’s Syndrome, and Myasthenia Gravis. Engineered to significantly prolong the dosing interval, LBL-047 presents an optimal product profile for subsequent clinical and commercial development.

Huang Xiao, Vice President of Discovery Research at Leads Biolabs, said: “EULAR is a highly anticipated event in the fields of rheumatology and immunology. We are honored to be featured in this prestigious gathering of over 18,000 experts and scholars from more than 130 countries to share the exciting data we have generated. LBL-047, independently developed and fully owned by Leads Biolabs, represents a significant achievement arising from our differentiated innovation strategy. Its unique design is based on our profound understanding of autoimmune diseases and target mechanisms, integrating extensive antibody engineering technologies and optimization efforts. We are very pleased with the results we have seen in preclinical studies. Leads Biolabs is dedicated to our corporate philosophy of ‘care for life, focus on innovation, and win-win cooperation,’ and is committed to providing safer and more effective treatment options for patients. Currently, LBL-047 is in the preclinical research stage, and we will continue to efficiently promote the development of this drug candidate to bring effective treatments to patients with autoimmune diseases as soon as possible.”

About LBL-047

B cells and pDCs play a crucial and synergistic role in the pathogenesis of many autoimmune diseases. Inhibiting the function of B cells and pDCs is a potential therapeutic strategy for treating various autoimmune diseases. LBL-047 is a long-acting TACI/anti- BDCA2 bispecific fusion protein, obtained by fusing an engineered TACI domain with a defucosylated anti-BDCA2 humanized monoclonal antibody.

TACI is the natural high-affinity receptor for B cell activation factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL), which are key cytokines that promote B cell and plasma cell survival, maturation, and function. Engineered TACI domain can be used to trap BAFF and APRIL, inhibiting B-cell function.

BDCA2 is specifically expressed on pDCs and BDCA2 agonist antibody can suppress the IFNs release. Additionally, anti-BDCA2 antibodies can directly eliminate pDCs through mechanisms such as ADCC, inhibiting pDC-mediated immune responses. The defucosylated anti-BDCA2 antibody has stronger ADCC activity, and the introduction of YTE mutation in the Fc region further prolongs the half-life of the antibody.

Preclinical studies have demonstrated that LBL-047 can potently inhibit the functions of B cells and pDCs simultaneously, and possesses excellent pharmacokinetic properties, indicating broad clinical applications and market prospects in the treatment of various autoimmune diseases.

About Leads Biolabs

Nanjing Leads Biolabs Co., Ltd. is a clinical-stage biotechnology company founded in Nanjing by a team of senior U.S.-trained antibody drug developers. Since 2014, Leads Biolabs has been dedicated to the discovery and development of novel antibody drugs with independent intellectual property rights for the treatment of oncology and other major diseases of high unmet medical needs, particularly the challenges in cancer immunotherapy. Our extensive R&D pipeline consist of more than twenty novel tumor immunotherapy, autoimmunity and ADC molecules based on monoclonal and bispecific antibody technology platforms. Leads Biolabs is committed to providing safe, effective, accessible, and affordable new drugs to address the unmet needs of patients around the world.

SOURCE: Leads Biolabs