VGT-1849B

VGT-1849B is an investigational antisense oligonucleotide (ASO) being developed by Vanda Pharmaceuticals for the treatment of polycythemia vera (PV), a rare chronic myeloproliferative blood disorder. The drug utilizes a proprietary backbone chemistry known as OliPass Peptide Nucleic Acid (OPNA), which is derived from peptide nucleic acid (PNA) and modified to enhance cell permeability and RNA affinity. VGT-1849B is designed to selectively target JAK2 mRNA, thereby reducing the production of the JAK2 protein, including the mutant JAK2 V617F variant found in over 95% of PV patients. Unlike existing JAK inhibitors that often target multiple members of the Janus kinase family, VGT-1849B is characterized as the first agent to be solely selective for JAK2, potentially offering an improved safety profile with fewer off-target kinase effects. The FDA granted Orphan Drug Designation to VGT-1849B in August 2025.