Capsid Assembly Inhibitors for HBV

1. Huge drug market for HBV

(1) In 2016 global HBV prevalence is 3.9%, with 292m cases, within which 32% of cases were in need of therapies. In 2017, 870,000 people have been dead from HBV. 25% of HBV patients develop HCC.

(2) Patients receiving Long-term treatment with the current therapies easily relapse after off-treatment. And uncleared HBsAg causes an unexpected immune reaction for a long time. A low functional cure rate is a big challenge for HBV therapy, and new strategies are in need to reform HBV therapy.

2. Capsid assembly inhibitors are a viable strategy for HBV

Capsid assembly inhibitors bind to the dimer-dimer interface and disrupt the formation of functional nucleocapsids, blocking several steps of the HBV life cycle including entry, replication, assembly and secretion and preventing the maturation of infectious viral particles.

3. A second general capsid assembly inhibitor with better anti-HBV activity than contemporary competitors in vitro.

(1) The EC50 and EC90 of asset are both at nanomolar lever, which are 10–100 times lower than that of competitors(AB-506, JNJ-379, NVR3-778 and HBI-0731) in vitro.

(2) Asset shows more potent inhibition of HBV replication, especially HBeAg and HBsAg in PHH infection model, compared with ETV.

4. Excellent active HBV ability in vivo.

(1) In the HDI mouse model, the asset shows a dose-dependently reduction of serum and liver HBV DNA, illustrating an excellent antiviral activity.

(2) The asset is more potent in reducing the viral antigen in vivo.

5. Good safety.

(1) Low CYP enzyme induction in preclinical study. The combination of asset and ETV in the phase IIb study accelerated HBV

(2) High safety window remains greater opportunity for curative combination therapy, which strategy is high up the functional cure rate.