Highlight

1. Clear MoA

(1) CLDN18.2 is a highly selective biomarker that is only expressed in differentiated gastric epithelial cells, not in undifferentiated gastric stem cells. And CLDN18.2 is highly expressed in several cancer tissue cells, including gastric cancer(60-80% positive rate), pancreatic cancer. Targeting CLDN18.2 antigen is a good strategy to treat gastric cancer.

(2) Compared to other treatment, CLDN18.2(nanobody) CAT-T is more effective with acceptable safety.

2. Huge unsatisfied demand

Gastric cancer is the fifth most common cancer in the world, with more than 1 million diagnosed patients worldwide each year. Its prognosis is poor, and most cases have already metastasized when diagnosed. Currently target therapies target PD1/PDL1(12-50% positive rate), HER2 (7.3-20.2% positive rate), and VEGF (72%). These therapies can not meet all patients’ needs.

3. High specific binding to CLDN18.2 antigen rather than CLDN18.1 antigen.

4. Excellent safety profile

1) in vitro: Asset could only be activated when cocultured with NUGC4 which expressing CLDN18.2. However, the benchmark also has a response to CLDN18.2 negative cells, such as Beas-2B cells and mouse lung cells.

2) in vivo: Asset has no effect on the weight of mice, while the benchmark causes a sharp decrease in mice weight. And asset is well tolerated and no infiltration to the lung and pancreas, which demonstrated better safety profile.

5. Great efficiency in tumor-bearing model

1) 2×10⁶ CLDN18.2 CAR-T cells are as effective as benchmark in PDX model, while being more safe. No mice died in asset 2M dose group and asset 6M dose group , But 50% mice died in benchmark 2M dose group.

2) CLDN18.2 CAR-T is only enriched in the tumor tissue in NUGC4 tumor- bearing mice.

Research progress

1) First CLDN18.2 VHH based CAR-T obtained IND approval by FDA and CDE, IIT is ongoing, and phase Ⅰ trial started in CN.

2) In FIH trial, patient(poorly differentiated adenocarcinoma of gastric antrum, radical gastrectomy with multiple abdominal metastasis), whose disease progressed after 2L treatment only received 1×10⁶/kg CAR-T cells of asset to reach SD. No DLT or SAE; No nausea or vomiting.