Highlights

1.Clear MoA- Restores T Cell Function through Inhibition on Adenosine Signaling Pathway

(1) The asset treatment results in decrease of pCREB, a downstream PD marker of adenosine signaling.

(2) The asset antagonizes the immunosuppressive effects by NECA (adenosine analogue) and results in rescue of IL-2 and TNF-α secretion from CD4+ T cells and CD8+ T cells, which suggests the recovery of anti-tumor effects of T cells.

2. Shows Significant Monotherapy Activity

(1) The asset shows anti-tumor effects in a dose-dependent manner in the mouse MC38-hPD-L1 colorectal tumor model.

(2) The asset shows better anti-tumor activity than AB928 at the same dose.

(3) The asset reduces Treg infiltrated in tumors.

3.Significant Synergy with Tecentriq(PD-L1 mAb)&Keytruda(PD-1mAb)

(1) The asset has comparable anti-tumor effects with Tecentriq& Keytruda (PD-L1 mAb) in the mouse MC38-hPD-L1 colorectal tumor model/ humanized HCC827 NSCLC model.

(2) Combo of the asset and Tecentriq& Keytruda shows significant synergy.

4.Non-clinical TOX Studies was observed

(1) In the pivotal 4-week repeated dose toxicity with a 4-week recovery period in SD rats and beagle dogs, animals in this asset treated group were well tolerated, and a good safety margin (3.6 vs. NOAEL in dogs, 25.9 vs. HNSTD in rats) was achieved.

(2) The IC50 of hERG current was >40 μM.

(3) Showed low risk for the cardiovascular, respiratory and central nervous system in safety-pharmacology studies.

(4) No genotoxicity was noted in the chromosomal aberration test in Chinese hamster lung fibroblasts.

(5) No genotoxic effect on CD-1 mice bone marrow cells was observed in mice bone marrow micronucleus study.

Research progress：

(1) Project Advantages：The fourth A2aR/A2bR inhibitor worldwide, with the characteristics of high activity, high selectivity and low toxicity.

(2) Patent Strategy :The core patents are expected to be filed in major countries in October 2022.(CN,PCT,US,EP,JP,CA,AU,FR,SG etc.)