BEPro Technology™ was developed to further improve efficiency of certain nucleotide prodrugs and can be used to deliver nucleotide analogs in efficiency and selectivity superior to ProTide technology. Key activation of BEPro prodrugs is achieved by certain esterase, and the technology can be used beyond the liver diseases. An example of BEPro Technology superiority in improving prodrug delivery efficiency of a nucleotide analog is summarized below by a published literature (AASLD 2021 #949 poster by Ligand Pharmaceuticals). Sofosbuvir (Sovaldi®, Gilead Sciences) is a nucleotide prodrug used as a component of combination antiviral regimens, Harvoni® and Epclusa®,  for the treatment of chronic hepatitis C infection. Sofosbuvir is converted in vivo into the nucleotide GS-331007 which is further phosphorylated to yield an active triphosphate. To demonstrate the BEPro Technology superiority, Sofosbuvir and its BEPro-version, LGN-5, were administered via intravenous (iv) or oral (po) administration to Sprague-Dawley rats and the blood nucleoside and liver triphosphate concentrations were analyzed and summarized in the following graph. The BEPro technology-enabled compound, LNG-5, demonstrated much higher efficiency in the delivery of active nucleotide to the liver and much better liver-selectivity than the corresponding ProTide prodrug, sofosbuvir. The BEPro technology can be an effective means by which to increase oral bioavailability and the therapeutic index of this chemical class of therapeutic agents.