April, 2022 - Keymed Biosciences (HKEX:02162) announced that the U.S. Food and Drug Administration (FDA) granted CMG901 Fast Track Designation as monotherapy for the treatment of unresectable or metastatic gastric and gastroesophageal junction cancer which have relapsed and/or are refractory to approved therapies. This is another milestone after CMG901 received Orphan-drug Designation from the FDA.
Among all the Claudin 18.2-targeted drugs, CMG901 is the first and only one which received this FDA designation so far. This designation was granted based on the phase 1 studies that assessed the safety, tolerability, pharmacokinetic (PK), and preliminary efficacy of CMG901. The dose-escalation stage of Phase I clinical trial of CMG901 in subjects with solid tumors is about to be completed in China, and the dose-expansion stage is expected to be initiated in the second quarter of 2022.
Fast Track Designation is one of the FDA's programs to accelerate the clinical development and review of new drugs to meet the unmet medical needs of serious diseases.
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.