Zhimeng Biopharma announces that it will present new anti-HBV data on its novel hepatitis B virus (HBV) nucleocapsid formation inhibitor CB-001 at the EASL-AASLD Joint Meeting on HBV Endpoints in London, March 8-9, 2019
Current drugs for chronic hepatitis B (NAs and IFNs) rarely provide a cure for patients. New classes of drugs that hit different virus targets are welcomed to bring a higher cure rate in finite treatment periods. We have discovered a novel series of pyrazole compounds as HBV nucleocapsid formation inhibitors (represented by CB-001). CB-001 is structurally distinctive from the current class I (heteroaryldihydropyrimidines, e.g., BAY-41-4109 and GLS4) and class II (phenylpropenamides and sulfamoylbenzamides, e.g., AT-130) HBV core protein allosteric modulators (CpAMs). We evaluated the antiviral activities of CB-001, class I, and class II compounds against a panel of viruses containing different mutations in HBV core protein including the core T109I mutant that has shown resistance to both NV-010-001 and BAY 41-4109 core protein modulators (Klumpp et al., PNAS 2015).
CB-001 accelerated the formation of capsid devoid of HBV pgRNA and DNA in a dose-dependent manner. When added at the time of virus infection of PHH, CB-001 inhibited HBV cccDNA formation and HBsAg level. In addition, when used in combination with IFN-alpha in PHH assay, CB-001 demonstrated an additive effect in inhibiting both HBsAg and DNA, while it only showed an additive inhibitory effect with Tenofovir on HBV DNA. Most importantly, CB-001 was highly active against a panel of viruses that contain mutations in core protein and that are resistant to classes I and II CpAMs.
The unique structure of CB-001 and its distinctive antiviral profile against core protein mutants distinguish itself from reported class I and class II HBV CpAMs. These characteristics of CB-001 warrant its clinic evaluation for treatment of chronic HBV infection.