Highlights:

1. Clear MoA.

1) LAG-3 belongs to the immunoglobulin (Ig) superfamily, it is a type I transmembrane protein with structural similarities to CD4.

2) LAG-3 is extensively expressed on activated T cells and NK cells，also expressed on activated B cells and plasma cell-like dendritic cells (pDCs).

3) LAG-3 is an inhibitory immune checkpoint for T cells, and like PD-1 and CTLA-4, LAG-3 negatively regulates the proliferation, activation, and homeostasis of T cells. It is a novel target for cancer and autoimmune disorders.

2. Excellent preclinical efficacy:

1) The binding activity of this LAG-3 mAb to human activated CD4 T cells is slightly higher than that of the positive control drug BH98 (Relatlimab analogue).

2) The blocking effect on FGL1 is higher than that of BH98.

3. Similar tumor-killing activity as Relatlimab (BH98) in vivo.

4. The combination of LAG-3 mAb and PD-1 can synergistically enhance the anti-tumor effect, better than monotherapy.

5. Excellent safety

1) NOAEL= 100 mg/kg.

2) No immunotoxicity: no ADCC activity

3) Plasma cytokine concentrations (IFNγ, TNFα, IL6, IL1β, IL2, IL4) were not abnormally increased after mAb administration.

4) No hemolytic effect.

Research progress：

1. Completed preclinical development

2. Phase I clinical trials are ongoing to evaluate the safety, tolerability, pharmacokinetics and efficacy of candidate antibodies for advanced malignancies.