RGX-202 is a small molecule that suppresses gastrointestinal cancer growth by inhibiting a novel cancer metabolism pathway involved in supplying energy to cancer cells.
Mechanism of Action
Creatine metabolism has been implicated in colon cancer progression and metastatic colonization of the liver. Cancer cells upregulate and release creatine kinase-B (CKB) into the extracellular space, where it generates the high energy metabolite phosphocreatine.
Phosphocreatine is imported via the creatine transporter SLC6a8, the target of RGX-202 that is over-expressed in several prevalent cancer types, including gastrointestinal cancers.
Intracellular phosphocreatine can be converted to ATP to fuel the survival of cancer cells as they proliferate and spread. Consistent with this finding, genetic depletion of SLC6a8 in colon and pancreatic cancer cell lines significantly reduced cancer growth in animal studies.1
RGX-202 is an investigational drug candidate. Pre-clinical research demonstrates that RGX-202 is active both as a single agent as well as in combination with standard-of-care therapies in several gastrointestinal cancer models.2 Oral administration of RGX-202 induces apoptosis (cell death) of colon cancer cells in mice. RGX-202 suppresses the growth of colorectal, pancreatic, and gastric cancers when used as a single agent in animal models, where it has also demonstrated enhanced activity in combination with chemotherapy.
Rgenix owns composition of matter and method of use patents covering RGX-202. A phase 1 study of RGX-202 in patients with gastrointestinal cancers, including colorectal and gastric cancer, will begin in mid-2018.
RGX-104 is a novel oral small molecule immunotherapy in development for the treatment of solid tumors, including drug-resistant malignancies.
1) Loo JM et al. Cell. 2015 Jan 29;160(3):393-406
2) Kurth I et al. Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, Illinois (IL)