Highlights

1.Clear MoA

(1) HER2 is overexpressed or mutate in 25% of breast cancer patients, according to TCGA data. Herceptin, a HER2 mAb, targeting HER2 overexpressing cancers have proven to be beneficial. However, approximately 70% of patients develop resistance to Herceptin, and some patients present with primary resistance, who are seeking for an after-Herceptin solution.

(2) The resistance of immunotherapy in HER2+ breast cancer occurs because of the formation of immunosuppressive TME primarily or secondarily. Her2xCD3 BsAb is an ideal strategy to overcome the immunosuppressive TME barrier.(3) Her2xCD3 BsAb redirect T cells to target HER2-expressing tumor cells and to eradicate HER2+ cancer cells. The advantage of the BsAb strategy is that T cell activation is independent of antigen specificity, and a large fraction of the T cells are activated.

2. Excellent pre-clinical result:

(1) This asset could bind to HER2 and CD3 simultaneously.

(2) Excellent safety and efficacy.

1) induces lower ADCC on HER2+ tumor cells and has no cytotoxic on CD3+ Jurkat Cell, comparing with anti-HER2 or anti-CD3 antibody, respectively.

2) able to kill HER2+ tumor cell lines and has little effect in HER2- tumor cell line.

3) dose-dependent induced IL-6 and TNFa in day 1 treatment, and no cytokine release was detected in the longer 72 days treatment in cyno monkey.

4) showed dose-dependent anti HER2+ tumor efficacy in vivo.

3. Excellent clinical result:

(1) Good tolerance and effective in anti-HER2 resistance patients in phase 1 study.

1) All the patients were refractory or relapsed from multiple lines of anti-HER2 treatment.

2) No patients experienced DLT. Only 1 out of 7 patients experienced Gr1 CRS and no CRS occurred after priming dose;

3) No neurotoxicity and immune suppression were observed during the DLT period, much safer than ADC; 4) DCR@100ug cohort = 66%(n=3); 1 PD, 2 SDs；