December 27, 2023 -- 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 pancreatic cancer by the U.S. Food and Drug Administration (FDA): one is BA1105, an innovative antibody; and the other is BA1301, an i🅷nnovative Antibody-Drug Conjugate (ADC).

Orphan drugs, also kn𒊎own as drugs for rare diseases, are drugs for preventing, treating or diagno🐼sing 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 United States next, and will also help to reduce the cost on their development and accelerate their clinical development and launch.

Pancreatic cancer is one of the deadliest cancers, and diagnosing and treating it is a major challenge in clinical practice. Data from the International Agency for Research on Cancer (IARC), which is part of the World Health Organization (WHO), shows that globally there were 49🐠6,000 new cases of pancreatic cancer and 466,000 people died of it in 2020, and specifically 57,000 new cases and 48,000 deaths were in the United States. Because the disease does not have clear symptoms early on, most patients are already in the middle and advanced stages upon diagnosis. The prognosis of advanced pancreatic cancer is extremely poor. It is mainly treated with palliative chemotherapy, which rarely produces positive outcome or improves prognosis in general. Therefore, targeted drugs are urgently needed in clinical practice to improve the outcomes.

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 pancrea൩tic cancer patients and 30% of esophageal cancer patients. This makes Claudin 18.2 a potential molecular target for anticancer drugs.

BA1105 is more potent thanks to ADCC enhancement

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 (ant꧃ibody-dependent cell-mediated cytot♛oxicity) enhancement technology. The drug is undergoing a Phase I clinical study in China.

The results from non-clinical studies show that BA1105 is highly active on xenoဣgraft 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 efficient and safe thanks to site-specific conjugation

BA1301, Boan Biotech's first ADC candidate to undergo clinical studies, is undergoing a Phase I clinical study in China. BA1301 employs a site-specific conjugation technique 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 excellent in 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 pancreatic cancer, and the tumor of the mouse can be completely eliminated at medium and high doses; 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 human and cynomolgus monkey plasma. It will provide a new treatment option for💎 pancreatic cancer patients.

Dr. Dou Changlin, R&D President and Chief Operating Officer of Boan Biotech, said:" Claudin18.2 has become a popular molecular target for cancer research in recent years due to its high selectivity and stable expression on specific tumors. At Boan Biotech, we are developing two types of products at the same time: monoclonal antibody and ADC. They can be reciprocal to each other as first- and second-line treatments for advanced pancreatic cancer. They also have the potential of being used in combination with our BA1104 (Nivolumab Injection, a biosimilar of Opdivo®) to increase efficacy. This approach can further increase the certainty of clinical development and create synergies for us in the marketplace going forward. Being granted the ODD reflects the FDA's recognition of the potential of BA1105 and BA1301 for the treatment of pancreatic cancer. We will speed up the clinical development of these two investigational drugs, so that patients across the globe can benefit from them as soon as possible."

Boan Biotech boasts in-house drug discovery platforms and has developed 7 differentiated investigational drugs targeting CD25, CEA/CD3, IL-4Rɑ, Claudin 18.2, CD228 etc. Technically, they include monoclonal antibodies, bispecific antibodies, and ADCs. In addition, it's worth noting that the development of Boan Biotech's two marketed biosimilars and four investigational biosimilars is the fastest or among the fastest in China, boasting a first-mover advantage for launch. 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 United States, 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.