Protein Arginine Methyl Transferase 5 (PRMT5) is a member of a family of enzymes involved in the methylation of arginine residues on histones and other cytosolic and nuclear proteins. Through arginine methylation of histones, transcription factors and the spliceosome complex, PRMT5 regulates the expression of genes involved in promoting cancer cell growth and survival. These include cell cycle genes, tumor suppressors, oncogenes, and genes involved in proliferation and signaling. Overexpression and increased enzymatic activity of PRMT5 are associated with poor outcome and decreased survival in multiple human cancer settings. Consistent with its role in promoting cancer, PRMT5 inhibition has been shown to decrease tumor growth in preclinical models. Therefore, PRMT5 is believed to serve as an important mediator of cancer progression and can be targeted to treat a range of solid tumors and hematological malignancies.
Prelude’s lead product candidates are designed to be oral, potent and selective inhibitors of PRMT5. Prelude’s first clinical candidate, PRT543, is currently in a Phase 1 trial in advanced solid tumors and select myeloid malignancies. Prelude is also advancing PRT811, a second PRMT5 inhibitor that was optimized for high brain exposure, in the dose-escalation phase of a Phase 1 clinical trial in solid tumors, including glioblastoma multiforme (GBM) and primary central nervous system lymphomas (PCNSL).