Views: 1096 Author: Site Editor Publish Time: 2023-12-08 Origin: Site
The annual meeting of the American Society of Hematology (ASH) is the largest and most comprehensive international academic event in the field of hematology in the world. The 65th annual meeting of ASH will be held in San Diego, USA from December 9 to 12, 2023. Nanjing Leads Biolabs (Leads Biolabs) will present the key pre-clinical research data for a T cell engager bispecific antibody LBL-034 targeting G protein-coupled receptor, class C group 5 member D (GPRC5D) during a poster session.
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LBL-034 is a novel bispecific antibody targeting GPRC5D and CD3 discovered using our proprietary T cell engager antibody technology platform “LeadsBodyTM” with global intellectual property rights owned by Leads Biolabs. LBL-034 selectively targets GPRC5D-expressing tumor cells, triggering conditional activation of T cells, leading to the specific killing of these tumor cells by the activated T cells. This unique mechanism enables LBL-034 to exhibit a potent anti-tumor efficacy while minimizing adverse effects, such as cytokine release syndrome (CRS) caused by nonspecific activation of CD3-expressing T cells.
Poster Number: 4672
LBL-034, a Highly Differentiated T-Cell Engaging Bispecific Antibody Targeting GPRC5D for the Treatment of Relapsed or Refractory Multiple Myeloma.
Developed using Leads Biolabs’ proprietary T cell engager platform called "LeadsBodyTM", LBL-034 features a unique 2:1 molecular structure whereby 2 arm bind the tumor associated antigen with high affinity and 1 arm binding CD3 with about 100-folds lower affinity.
Using immunofluorescence and confocal microscopy, LBL-034 demonstrated remarkable T-cell redirection and bridging of GPRC5D-positive cells with CD3 expressing T cells, as well as the formation of immune synapses.
LBL-034 effectively induced cytotoxicity against multiple myeloma cells expressing GPRC5D at various levels, promoted T-cell activation and secretion of IFN-γ/TNF-α.
Conditional T cell activation only happens when LBL-034 is targeting the GPRC5D-expressing tumor cells, resulting in localized secretion of cytokines and the killing of tumor cells.
LBL-034 has a strong bystander killing effect: In the presence of tumor cells with high expression of GPRC5D LBL-034 can also effectively kill tumor cells with low or no expression of GPRC5D.
LBL-034 exhibited superior anti-tumor efficacy compared to other GPRC5D T cell engager bispecific antibodies in a study using the human multiple myeloma cell line NCI-H929 xenograft mouse model with human PBMCs. Notably, LBL-034 triggered low levels of cytokine release and did not lead to a significant reduction in the body weight of mice, suggesting an excellent safety profile.
LBL-034 showed strong anti-tumor effects in mouse tumor models with both high and low GPRC5D expression, and displayed more favorable pharmacokinetic characteristics than the competing antibody.
The first-in-human investigational new drug (IND) applications of LBL-034 were approved by both the Chinese National Medical Products Administration (NMPA) on July 20th 2023 and by the U.S. Food and Drug Administration (FDA) on July 28th, 2023. Extensive preclinical research strongly supports that LBL-034 has the potential to be best in class. LBL-034 is currently undergoing a phase I clinical trial in China.
Dr. Hong Ling, Senior Vice President and Chief Scientific Officer of Leads Biolabs, introduced: "LBL-034 is a CD3 bispecific targeting GPRC5D developed by Leads Biolabs using our proprietary technology platform, “LeadsBodyTM”. It possesses unique molecular design and mechanisms of action that enhance the killing of tumor cells while reducing cytokine release and T-cell exhaustion. In both in vitro and in vivo experiments, LBL-034 has demonstrated potent anti-tumor efficacy. Currently, LBL-034 has obtained IND approvals in China and the United States and is undergoing Phase I clinical studies in China. We hope that LBL-034 will bring more benefits and choices to cancer patients around the world."
G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) is a 7-pass transmembrane receptor protein that is selectively overexpressed on malignant plasma cells of multiple myeloma and low in normal tissues or cells. The intensity of GPRC5D expression is an independent prognostic factor in multiple myeloma, and its overexpression is significantly associated with reduced overall survival. These indicating that GPRC5D may be a novel target for anti-MM therapy.
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.