Highlights:

1. Clear MoA.

1) CLDN18.2 is a tight-junction protein, and is typically buried in gastric mucosa. But anti-CLDN18.2 macromolecular drugs can not bind to it due to cell tight junction function in normal tissues.

2) CLDN18.2 is highly expressed in some cancer, such as gastric cancer, pancreatic cancer and lung cancer.

3) CLDN18.2 positive cancer cells’ connection is loose. So it makes antibodies more easily bind to the CLDN18.2.

2. Address unmet clinical needs:

1) CLDN18.2 is a promising target among HER-2 negative gastric cancer, not only on high selectivity, but also on population prevalence. Besides, the survival period of patients diagnosed with solid cancer such as gastric cancer is too short. The present medicine can’t improve patients’ benefits.

2) Many cancers are low immunogenicity, such as pancreatic cancer, which has few or no CD8+ T cells around the tumor cell or in the tumor microenvironment. Anti-PD1/PD-L1 is not effective for treating those tumors, but CLDN18.2 × CD8+ T bsAb can increase CD8+ T cells to treat them.

3. CLDN18.2 × CD8+ T bsAb has a high affinity. Its affinity is higher than IMAB362.

4. High tumor-killing activity in vitro

5. High tumor-killing activity in vivo

1) BsAb shows significant in vivo efficacy at a low dose (0.1 mpk)

2) The efficacy lasts for more than 24 days, only given two doses (0.1 mpk) on day 1 and day 3.

6. T1/2=40 h

Research progress：

1. The phase 1 trial in advanced solid tumors is ongoing (accelerated titration starting from 0.01 mpk combined with a BOIN design).

2. In the expansion part, two cohorts of 10 CLDN18.2+ pancreatic cancer patients are planned for the treatment of bsAb alone or bsAb in combination with chemotherapy.

3. CLDN18.2 × CD8+ T bsAb has great tumor-killing activity both in CT26 cell-bearing model and tumor recurrence model.