2 CLDN 18.2-Targeted Drugs Granted ODD for Gastric Cancer in US

Boan Biotech today announced that two of its Claudin18.2-targeted investigational drugs have been granted the Orphan Drug Designation (ODD) for the treatment of gastric cancer (including cancer of gastroesophageal junction) by the U.S. Food and Drug Administration (FDA): one is an antibody codenamed BA1105, and the other is an Antibody-Drug Conjugate (ADC) codenamed BA1301. Previously, BA1105 and BA1301 had been granted the ODD by the FDA for the treatment of pancreatic cancer.

Orphan drugs are drugs for preventing, treating or diagnosing rare diseases, so they are also known as drugs for rare diseases. Being designated as orphan drugs will help to get policy support for the development, registration and commercialization of BA1105 and BA1301 in the U.S., and will also help to reduce their R&D costs and accelerate their clinical development and launch.

Dr. Dou Changlin, R&D President and Chief Operating Officer of Boan Biotech, said: "The two investigational drugs targeting Claudin18.2, which were previously granted the ODD for the treatment of pancreatic cancer in the U.S., have now also been granted the ODD for the treatment of gastric cancer, including cancer of gastroesophageal junction, indicating the FDA’s preliminary recognition of their potential for the new indications. Gastric cancer is considered a rare disease in the U.S., but a major public health threat in Asia, including China. Currently, the overall treatment outcomes for gastric cancer are not satisfactory, and there are limited treatment options available, so there is an urgent need to develop new targeted therapies for it. Boan Biotech is committed to addressing the unmet medical needs of patients around the world. We will accelerate the clinical development of BA1105 and BA1301, so that patients can benefit from them as soon as possible."

Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer deaths worldwide¹. It is estimated that the global burden of gastric cancer will increase 1.6 times in terms of incidence and 2 times in terms of mortality by 2040². Advanced gastric cancer currently is mainly treated with the palliative systemic chemotherapy, which generally has very poor outcomes and prognoses. In addition, there are limited second-line treatments available for the advanced gastric cancer, and systemic chemotherapy is less specific. 

Claudin 18.2 is a transmembrane protein involved in regulating the tight junction between cells, which can be continuously and stably expressed on digestive tract tumors. Research shows that Claudin18.2 is expressed in 70% of gastric cancer patients, 50% of pancreatic cancer patients and 30% of esophageal cancer patients. This makes Claudin 18.2 a potential molecular target for anticancer drugs.

BA1105 is a human anti-Claudin18.2 recombinant IgG1 monoclonal antibody for treating Claudin18.2-positive advanced solid tumors. It is more potent thanks to the adoption of the ADCC (antibody-dependent cell-mediated cytotoxicity) enhancement technology. The drug is undergoing a Phase 1 clinical study in China. The results from non-clinical studies show that BA1105 is highly active on xenograft mouse models of Claudin18.2-positive human pancreatic cancer and gastric cancer when used alone or in combination with chemotherapy; BA1105 is 10-fold more potent than the reference antibody against cancer cells on tumors expressing different levels of Claudin18.2, and is also effective on tumors expressing low levels of Claudin18.2.

BA1301 is an ADC targeting Claudin18.2. It is also undergoing a Phase 1 clinical study in China. BA1301 employs a site-specific conjugation mechanism to conjugate a cytotoxic payload with a monoclonal antibody targeting Claudin 18.2. This directs the cytotoxic payload towards tumors by leveraging the targeting capability of the antibody. Such a design reduces the side-effects of the cytotoxic payload and improves the therapeutic window. The results from non-clinical studies show that BA1301 is very good at internalization and bystander killing, and has demonstrated an exceptional anticancer activity on tumor models expressing Claudin18.2. It can significantly inhibit the growth of a mouse xenograft of the Claudin18.2-positive human gastric cancer, and the tumor in the mouse can be eliminated at relatively low doses. BA1301 is also effective on tumors with low and medium Claudin18.2 expressions. BA1301 is safe and well-tolerated in animals -- its small-molecule toxins are stably conjugated, with a very low release ratio of no more than 0.05% in the plasma of humans and cynomolgus monkeys.

Boan Biotech has developed 6 differentiated investigational drugs targeting CD25, CEA/CD3, IL-4Rɑ, Claudin 18.2, and CD228 on its own drug discovery platforms. Based on the roadmaps for their development, they include monoclonal antibodies, bispecific antibodies, and ADCs. In addition, it's worth noting that Boan Biotech was the fastest or among the fastest in China in developing its two marketed biosimilars and four investigational biosimilars, and enjoyed the first-mover advantage to launch them. Besides, the company is also seeking to register some candidates in its pipeline or conduct clinical trials for them in developed markets such as Europe, the U.S., and Japan. The above-mentioned innovative drugs and biosimilars are developed closely revolving around the needs in clinical practice both at home and abroad, to form a strong portfolio for the company.