Leads Biolabs will present two innovative researches at AACR Annual Meeting 2024, introducing newly discovered bispecific or monoclonal antibodies with the potential to treat hematologic malignancies

American Association for Cancer Research^® (AACR) annual meeting is the largest cancer research conference in the world. The 2024 AACR annual meeting will be held in San Diego, USA, from April 5th to 10th to share the latest advancements in cancer and related biomedical sciences. Nanjing Leads Biolabs (Leads Biolabs) will unveil two latest innovative antibodies during a poster session, including LBL-043, a novel bispecific antibody targeting LILRB4×CD3 for treating hematologic malignancies, and LBL-049, a GDF-15 neutralizing antibody for treating cancer cachexia.

LBL-043, a novel LILRB4×CD3 T cell engager, for the treatment of LILRB4 positive AML and MM

LILRB4 belongs to the LILRB family, it is a type I transmembrane protein consisting of two extracellular Ig domains, a transmembrane domain, and three cytoplasmic ITIM motifs, involved in downregulating immune responses. LILRB4 is highly expressed on leukemia cells of the M4 and M5 (FAB classification) subtypes, while it is not expressed on normal hematopoietic stem cells. Compared to other leukemia markers, LILRB4 exhibits better specificity, making it an ideal target for leukemia therapy. Additionally, LILRB4 has been reported to be highly expressed in multiple myeloma (MM), making it a potential target for multiple myeloma treatment.

LBL-043 is a bispecific antibody targeting LILRB4 developed using Leads Biolabs’ proprietary CD3 bispecific technology platform, LeadsBody^TM, with unique molecular design and mechanism of action. LBL-043 can specifically target and kill cells expressing LILRB4, demonstrating potent killing effects on tumor cells with either high or low LILRB4 expression. In mouse tumor models, LBL-043 significantly prolonged mouse survival. In cynomolgus monkey dose exploration experiments, LBL-043 showed good tolerability. Overall, these findings suggest promising prospects for LBL-043 in the treatment of acute myeloid leukemia (AML) and MM.

LBL-049: A novel neutralizing antibody against GDF15 for the treatment of ocachexia

Cachexia is a disease characterized by weight loss, accompanied by a decrease in skeletal muscle and fat tissue, occurring in many diseases, especially in the progression of cancer. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor β superfamily. GDF15 can bind to the glial cell-derived neurotrophic factor family receptor α-like (GFRAL) protein, which is mainly expressed in the hindbrain. This interaction can activate the GFRAL-RET signaling pathway, transmitting anorectic signals, leading to weight loss, affecting fat and muscle degradation, and inducing cachexia. Anti-GDF-15 antibody may potentially reverse this response, making it an important therapeutic target for cachexia.

LBL-049 is a novel humanized GDF-15 neutralizing antibody developed by Leads Biolabs, which has high protein binding affinity, and can more effectively block GDF15/GFRAL signaling. LBL-049 has shown stronger efficacy and better specificity in preclinical experiments compared to competitor’s antibody. In two mouse cachexia models respectively induced by tumor or chemotherapy, LBL-049 successfully prevented weight loss in mice and significantly reduced levels of circulating free GDF15 protein, outperforming the competitor’s antibody. Furthermore, LBL-049 demonstrated excellent pharmacokinetic properties in rats and will be also developed for subcutaneous formulation, showing excellent druggability. The results suggest that LBL-049 has clinical potential in treating tumor cachexia and other GDF-15 associated diseases.

Dr. Hong Ling, Senior Vice President and Chief Scientific Officer of Leads Biolabs, said "Targeting LILRB4, the CD3 bispecific antibody LBL-043 is another CD3 engaging bispecific antibody developed through LeadsBody^TM's proprietary technology platform, following the company's clinical-stage projects LBL-033 (MUC16/CD3) and LBL-034 (GPRC5D/CD3). It has completed preclinical stage PCC development and preliminary monkey toxicology experiments. It is aimed at particularly addressing the lack of effective drugs for AML, as well as drug resistance or relapse in MM. Another promising development is Leads Biolabs' anti-GDF15 neutralizing antibody, which is used to treat cachexia often accompanying advanced or chemotherapy-treated tumor patients, as well as muscle and fat degradation accompanying other neurometabolic diseases and anorexia. These new achievements demonstrate Leads Biolabs' drug discovery of being clinically-oriented, science-driven, and technology-based philosophy and approach. Look forward to these projects entering clinical development as soon as possible, bringing superior clinical benefits and more therapeutic options for patients.”

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.