Highlights:

1. Clear MoA.

1) Dual-blockade of PD-1 and SIRPα can activate potent antitumor effects via both innate and adaptive immune responses.

2) Anti-SIRPα drugs are a potential treatment for solid cancer because they can more easily enter into the solid tumor microenvironment through binding to peripheral macrophages.

3) SIRPα is only expressed on myeloid cells, not on erythrocytes. Unlike anti-CD47 drugs, Anti-SIRPα drugs do not cause erythrocytopenia.

2. High affinity.

The bsAb has high selectivity and high affinity to SIRPα and PD-1.

3. The bsAb can bridge PD-1 and SIRPα positive cells, while single or combination of antibodies can’t.

4. bsAb simultaneously release the inhibitory activity of DCs, T cells, and macrophages.

5. Better anti-tumor activity in vivo.

1) Excellent antitumor activity.

2) Great tumor immune memory in tumor recurrence model.

3) bsAb can polarize macrophages (decreased M2, increased M1) in the tumor microenvironment.

6. CMC ready: high purity (SEC ≥ 99%), good stability, great druggability.

Research progress：

a) CMC stage: pilot production and toxicity test.

b) The bsAb binds specifically to SIRPα and PD-1 with high affinity.

c) The combination of SIRPα and PD-1 shows better activity than solitary target in vivo and remains active in the recurrence model due to great immune memory.