Keymed Biosciences announced that its new drug candidate CMG901 (the “Claudin 18.2 antibody drug conjugates”) for the treatment of gastric cancer and gastroesophageal junction adenocarcinoma has been granted the Orphan-drug Designation by the Food and Drug Administration of the United States (the “FDA”) recently. Previously, in March 2021, the Company received the clinical trial application approval of CMG901 from the FDA for the clinical trial in gastric cancer and gastroesophageal junction adenocarcinoma in the United States.

“The ongoing Phase 1 trial of CMG901 demonstrated promising anti-tumor activity in advanced gastric and GEJ adenocarcinoma patients,” said Joy Yan, MD, PhD, Keymed Biosciences Chief Medical Officer, “We look forward to working closely with the FDA to finish the design of the global pivotal trial in Claudin 18.2-positive advanced gastric and GEJ adenocarcinoma”.

About CMG901

CMG901 is the first Claudin 18.2 ADC to obtained IND approval in China and in the U.S. CMG901 consists of three components: a monoclonal antibody targeting Claudin 18.2, a cleavable linker and a potent cytotoxic payload (MMAE). Claudin 18.2 has been identified as a highly selective molecule that is widely expressed in multiple solid tumors, including gastric cancer and pancreatic cancer, suggesting that Claudin 18.2 is an ideal target for tumor therapeutic development.

CMG901 can cause tumor cell death by several mechanism:

■ CMG901 binds to Claudin 18.2 positive cell via its monoclonal antibody portion. After binding, CMG901 will be internalized into lysosome by tumor cells and release the cytotoxic payload, leading to cell cycle arrest and apoptosis of the tumor cells.

■CMG901 can stimulate cellular and soluble immune effectors that activate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to destroy the Claudin 18.2 positive cells.

Preclinical studies suggest that CMG901 can effectively kill gastric cancer cells with much stronger antitumor potency than zolbetuximab analog or the unconjugated antibody of CMG901. Meanwhile, CMG901 also shown good tolerance and favorable safety profile in preclinical studies.

About gastric cancer

Globally, there are more than 1 million new cases of gastric cancer and about 769,000 deaths per year, and China accounts for 43.9% of the global incidence and 48.9% of the mortality rate. Because of the atypical early symptoms of gastric cancer, 80%-90% of gastric cancer patients are already in the progressive stage when they are first diagnosed. The 5-year survival rate after surgery for progressive gastric cancer is 35.9%, and the overall recurrence rate is as high as 50%-70%.

Gastric cancer is highly heterogeneous, and there is a lack of targeted therapeutic drugs. Now only targeted drugs for HER2 are approved and marketed, but HER2-positive mutant type in gastric cancer accounts for only 10%-20%, and there is still a huge unmet clinical need with a large limitation of the applicable patient population. Claudin 18.2 is highly expressed in 60% of gastric cancers. Targeting Claudin 18.2 will likely provide a more promising novel treatment for gastric cancer.