RC118, an antibody-drug conjugates or ADC being developed by RemeGen, a commercial-stage biotechnology company based in Yantai, China, has been granted two orphan drug designations by the U.S. Food and Drug Administration (FDA) for gastric cancer (including gastroesophageal junction cancer) and pancreatic cancer. Having previously been twice granted orphan drug designations, one for Disitamab Vedotin (爱地希®/Aidixi®; Previously known as RC48), a novel HER2-targeted ADC, and one for Telitacicept (RC18) earlier 2022, this marks the fourth such designation RemeGen received.
Developed in-house, RC118 is RemeGen’s latest advanced ADC used to treat patients with solid tumors positive for Claudin 18.2 expressions. The investigational agent is composed of a recombinant humanized anti-CLDN18.2 antibody and monomethyl auristatin E (MMAE), a potent tubulin binder with a half maximal inhibitory concentration (IC50) in the subnanomolar range, conjugated through a cathepsin cleavable linker at an optimized drug–antibody ratio (DAR). The product was previously approved by China’s National Medical Products Administration (NMPA) Center for Drug Evaluation (CDE) to conduct clinical trials on September 18, 2021.
Phase 1 clinical trials for malignant solid tumors RC118 are currently being developed in Australia and China for the treatment of locally advanced unresectable or metastatic disease in patients with positive Claudin 18.2 expressions and a dose-escalation study is underway, thus far showing good safety and tolerability.
An interesting target
Claudin protein is a tight junction molecule whose function is mainly to regulate the permeability of the cellular barrier structure. As a member of the Claudin protein family, Claudin 18.2 (CLDN18.2) protein, an isoform of claudin18, is a member of the tight junction protein family, and is a highly tissue-specific protein that is mainly expressed in gastric epithelial cells and is also highly expressed in primary malignant tumors such as gastric, breast, colon, liver, and pancreatic cancers. 
Due to specific expression characteristics, Claudin 18.2 has become a popular target that many pharmaceutical companies have been paying close attention to.
Although no drug for this target have so far being approved, a number com companies are developing drugs designed to target Claudin 18.2. For example, EO-3021 (SYSA1801) is a potential best-in-class ADC being developed by Elevation Oncology. This company entered into an exclusive license agreement with CSPC Megalith Biopharmaceutical Co., a subsidiary of CSPC Pharmaceutical Group Limited to develop and commercialize EO-3021 (SYSA1801).
Another development program includes zolbetuximab (claudiximab, IMAB362), an investigational first-in-class chimeric antibody against Claudin 18.2 being developed by Ganymed Pharmaceuticals (now part of Astellas Pharma)
Orphan drugs, also known as rare disease drugs, are used for the prevention, treatment, and diagnosis of rare diseases. The orphan drug designations granted by the US FDA is applicable to drugs and biologics for rare diseases with less than 200,000 patients in the United States each year. The drugs that have been certified can potentially enjoy tax incentives in the United States, a seven-year market exclusivity period after listing, as well as other policy incentives.
“It is another positive step forward in the biotechnology development for RemeGen. We are very pleased to have received from the FDA the Orphan Drug Designation for gastric cancer and pancreatic cancer, which adds to the designation granted already for the treatment of myasthenia gravis,” noted Jianmin Fang, Ph.D., the Chief Executive Officer and Chief Scientific Officer of RemeGen.
RemeGen, founded in 2008, is one of a handful of Chinese biopharmaceutical companies with a fully integrated ADC platform. Based on this platform, the company has continuously improved and optimized its proprietary ADC product pipeline, with no less than four products, including the latest RC118, entering clinical trials or gaining marketing approval. Among them, China’s first domestically produced ADC drug, Disitamab Vedotin (RC48), with two indications for gastric and urothelial cancers and autoimmune drug Telitacicept (RC18) have been approved by NMPA in China.
A Study of RC118 in Patients With Locally Advanced Unresectable/Metastatic Solid Tumours – NCT04914117
A Study of RC118 in Patients With Locally Advanced Unresectable or Metastatic Malignant Solid Tumors – NCT05205850
 Cao W, Xing H, Li Y, Tian W, Song Y, Jiang Z, Yu J. Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. Biomark Res. 2022 May 31;10(1):38. doi: 10.1186/s40364-022-00385-1. PMID: 35642043; PMCID: PMC9153115.
Featured image: RemeGen’s Laboratories. Photo courtesy: © 2020 – 2023 RemeGen. Used with permission