Currently, there are over 250 million individuals world-wide who are chronically infected with hepatitis B virus (HBV) who are at risk from complications due to liver disease and liver cancer. HBV infection is currently managed with nucleos(t)ide reverse transcriptase inhibitors (NrtIs) that suppress HBV DNA replication and normalize alanine aminotransferase (ALT) levels leading to significant reductions in morbidity and mortality. Unfortunately, however, these agents are not curative and patients exhibit poor off-treatment responses that require indefinite therapy.
One of the most promising strategies under investigation are the core protein allosteric modulators (CpAMs) that block HBV replication at multiple steps in the viral lifecycle. Using a structure-based drug design approach, we have identified a series of CpAMs that exhibit best-in-class antiviral activity and possess excellent DMPK and safety properties.
Venatorx has nominated VNRX-9945 as a Development Candidate and advanced into IND-enabling pre-clinical toxicology studies to ready the compound for first-in-human testing in healthy volunteers and HBV infected patients.