Known as PRT543 while in testing, this targeted treatment molecule is among the first in an emerging class of drugs called PRMT5 inhibitors.
Protein arginine methyltransferases (PRMTs) are a family of enzymes that regulate a variety of cellular functions. When dysregulated, PRMTs are associated with several aggressive human cancers, including diffuse large B-cell and mantle cell lymphoma, pancreatic cancer and glioblastoma. Research published by the OSUCCC – James and other institutions suggests that PRMT5, a member of this family, is a potential oncoprotein involved in transforming a normal cell into a cancer cell and could be an important target for new treatment strategies.
The OSUCCC – James is one of four cancer centers participating in this first-in-human trial, which will enroll 100 patients across the United States. Patients age 18 or older with metastatic or advanced solid tumors, advanced diffuse large B-cell lymphoma, advanced mantle cell lymphoma, relapsed myelodysplastic syndrome or relapsed myelofibrosis may qualify.
Led by Robert Baiocchi, MD, PhD, the OSUCCC – James research team was the first to discover PRMT5 as a cancer driver and the first to develop and report a series of novel molecules to selectively inhibit it. The team has been evaluating PRMT5 inhibitors for the therapeutic treatment of various cancers, as well as benign blood and autoimmune diseases. The targeted molecule currently in testing (PRT543) was developed by Prelude Therapeutics, which is sponsoring the trial.
With support from the Drug Development Institute, a translational accelerator embedded within the OSUCCC – James, this entire portfolio of molecules was licensed to Prelude in 2016. The company is developing drugs that inhibit a specific enzyme (PRMT5) for cancer and other unmet medical needs. Prelude provides financial support for preclinical and clinical research conducted at the OSUCCC – James.
“PRMT5 is a compelling therapeutic target because it acts like a hub that coordinates diverse molecular activities for cancer cells,” Baiocchi says. “PRT543 selectively targets PRMT5. If proven effective in clinical testing, this could radically improve how we treat certain aggressive, recurrent cancers.”