Leads Biolabs will present four innovative researches at AACR Annual Meeting 2025

The 2025 American Association for Cancer Research^® (AACR) annual meeting will be held in Chicago, USA, from April 25 to 30. Nanjing Leads Biolabs (Leads Biolabs) will unveil the latest research results of four preclinical pipelines during a poster session, including LBL-054-CD3 (an anti-CDH17 and CD3 bispecific antibody), LBL-054-ADC (a novel hydrophilic CDH17-targeting antibody-drug conjugate), LBL-043 (a novel LILRB4xCD3 T cell engager) and LBL-058 (a novel T cell engager conjugate).

【Abstract Title】LBL-054-CD3: An anti-CDH17 and CD3 bispecific antibody for the treatment of CDH17-positive gastrointestinal cancer

LBL-054-CD3 is a novel bispecific antibody targeting CDH17 and CD3 to selectively kill CDH17-positive tumor cells by engaging T cells. LBL-054-CD3 was developed using our proprietary LeadsBody™ T-cell engager platform, comprising high-affinity arms targeting CDH17 and one finely tuned arm targeting CD3, engineered to balance efficacy and safety characteristics.

LBL-054-CD3 was shown potent binding affinity for CDH17 with no cross-reactivity to other family proteins. In vitro cytotoxicity assays revealed that LBL-054-CD3-mediated tumor cell killing was dependent on CDH17 expression level, inducing moderate cytokine release and cell proliferation while exhibiting no cytotoxic effects on CDH17-negative cells. Further, the bispecific antibody is shown excellent antitumor activity in both in vitro and in vivo experiments.

【Abstract Title】Novel hydrophilic CDH17-targeting antibody-drug conjugate exhibits anti-tumor efficacy in preclinical xenograft models

LBL-054-ADC is a novel CDH17-targeting antibody drug conjugate (ADC) that is developed from a humanized CDH17 IgG1 monoclonal antibody conjugated with our proprietary linker-payload platform. LBL-054-ADC exhibited proper affinity, and rapid internalization. In the killing assays LBL-054-ADC was more potent with CDH17 positive cancer cells while less prone to kill CDH17 negative cells. And also, LBL-054-ADC exhibited stronger bystander effect, high stability in plasma, robust anti-tumor activity and good tolerability in vitro and in vivo experiments.

【Abstract Title】LBL-043, a novel LILRB4xCD3 T cell engager, for the treatment of relapsed/refractory multiple myeloma

LBL-043 is a bispecific antibody targeting LILRB4 developed using Leads Biolabs’ proprietary CD3 bispecific technology platform, LeadsBody™, 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 demonstrated significant tumor inhibitory effects.‌ In cynomolgus monkey dose exploration experiments, LBL-043 showed good tolerability with a maximum non-severe toxic dose of 10 mg/kg. Overall, these findings suggest promising prospects for LBL-043 in the treatment of multiple myeloma (MM).

【Abstract Title】LBL-058, a novel T cell engager conjugate (TEC) targeting DLL3 with dual tumor suppressive functions

LBL-058, which was developed using our proprietary linker-payload platform, comprised of a DLL3-targeted T cell engager conjugated to a novel topoisomerase I inhibitor (TOP1i) payload. Moreover, LBL-058 was designed with a higher affinity targeting DLL3 and a lower affinity targeting CD3 to avoid potential cytotoxicity to T cells mediated by binding to T cells.

LBL-058 not only induce potent TDCC and T cell activation but also selectively deliver cytotoxicity payload to DLL3-positive tumor cells. In animal models, LBL-058 treatment induced durable tumor regression in xenograft tumor model. LBL-058 has the potential to be a First-In-Class DLL3-targeted TCE ADC, which combines the anti-tumor properties of TCE and ADC, and shows a potent and durable anti-tumor activity and is expected to provide clinical benefits for the treatment of patients with SCLC.

About CDH17

CDH17 is a member of the cadherin superfamily, a group of calcium-dependent cell adhesion molecules critical for organ development, tissue integrity, and cancer progression. In normal tissues, CDH17 is highly restricted to the lateral membrane and concealed within intestinal tight junctions, making it inaccessible and blocking immune cell infiltration. In contrast, it is overexpressed and redistributed in 50% to 90% of gastrointestinal cancers, leading to its exposure on the cancer cell surface，therefore becoming more accessible to target. This unique feature makes CDH17 a promising target for antibody-based therapies.

About LILRB4

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 MM, making it a potential target for multiple myeloma treatment.

About DLL3

Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in small cell lung cancer (SCLC) and other neuroendocrine tumors, and its expression is limited in normal cells. Nowadays, many DLL3-targeting therapies are in development. Among them, Tarlatamab, which is a TCE, has been approved by FDA for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. At the same time, several DLL3 targeting ADCs were also showing some promising results. Thus makes DLL3-targeting therapy an attractive strategy to treat SCLC.