Leads Biolabs Presents Preclinical Data on LBL-047 at EULAR 2024 Congress

Nanjing Leads Biolabs Co., Ltd. (Leads Biolabs), a notable biotechnology company, recently made a significant impact at the European League Against Rheumatism (EULAR) Congress in Vienna, Austria. The company presented its pioneering therapeutic candidate, LBL-047, which has demonstrated promising results in preclinical studies.

LBL-047 is a first-in-class, long-acting TACI/BDCA2 bispecific antibody fusion protein. It combines a Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI) domain with an antibody that targets Blood Dendritic Cell Antigen 2 (BDCA2). These components work together to inhibit B cell and plasma cell functions and deplete interferon-secreting plasmacytoid dendritic cells (pDCs). This dual action helps mitigate autoimmune activity effectively. Additionally, a YTE mutation in the Fc region of the antibody extends its half-life, enabling less frequent dosing and improved patient compliance.

In multiple preclinical experiments, LBL-047 has shown impressive activity and pharmacokinetic properties. Notable achievements include significant inhibition of interferon-alpha (INF-α) release, robust depletion of pDCs in both in vitro and in vivo settings, and superior inhibition of B cell and plasma cell functions compared to existing TACI fusion proteins. In an Experimental Autoimmune Encephalomyelitis (EAE) mouse model, which simulates multiple sclerosis, LBL-047 significantly alleviated clinical symptoms and inhibited B cell and plasma cell functions. Moreover, in cynomolgus monkeys, LBL-047 demonstrated an excellent pharmacokinetic profile and substantially reduced levels of IgM, IgA, and IgG for up to six weeks.

These findings suggest that LBL-047 could be a potent treatment for a variety of autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Lupus Nephritis (LN), Sjogren's Syndrome, and Myasthenia Gravis. Its ability to prolong the dosing interval makes it a highly desirable candidate for clinical and commercial development.

Huang Xiao, Vice President of Discovery Research at Leads Biolabs, expressed his enthusiasm at the EULAR Congress, acknowledging the event as a prestigious gathering of over 18,000 experts and scholars from more than 130 countries. Xiao highlighted that LBL-047, independently developed and fully owned by Leads Biolabs, is a testament to the company's innovative strategy and profound understanding of autoimmune diseases and their mechanisms. He elaborated on the company's commitment to innovation and cooperation, aiming to provide safer and more effective treatment options for patients. Huang Xiao also mentioned that LBL-047 is currently in the preclinical research stage, and the company is dedicated to advancing its development efficiently.

The mechanism behind LBL-047's effectiveness lies in its composition. B cells and pDCs play a crucial role in the pathogenesis of many autoimmune diseases. By inhibiting their functions, LBL-047 offers a therapeutic strategy for treating these conditions. The TACI domain in LBL-047 can trap BAFF and APRIL, cytokines that promote the survival and function of B cells and plasma cells. The BDCA2 component, on the other hand, is specifically expressed on pDCs and can suppress interferon release. Additionally, the anti-BDCA2 antibodies can eliminate pDCs through antibody-dependent cellular cytotoxicity (ADCC), further inhibiting immune responses. The defucosylated anti-BDCA2 antibody has stronger ADCC activity, and the YTE mutation prolongs the antibody's half-life.

Leads Biolabs, founded in Nanjing by a team of senior U.S.-trained antibody drug developers, has been dedicated to the discovery and development of novel antibody drugs since 2014. The company's extensive R&D pipeline includes over twenty innovative molecules targeting tumor immunotherapy, autoimmunity, and antibody-drug conjugates (ADCs). Leads Biolabs aims to provide safe, effective, accessible, and affordable new drugs to meet the unmet medical needs of patients worldwide.