Vonafexor (EYP001) in HBV



Jan-2019

HBV cccDNA

Hepatitis B virions enter hepatocytes through the binding of its surface protein to two cellular receptors, the heparan sulfate proteoglycans and to the bile salt transporter NTCP expressed at the basolateral membrane of hepatocytes. Viral capsids migrate to nuclear pores and the genome is released in the nucleus where the circular, partially double stranded DNA viral genome is completed and closed to form the cccDNA. The cccDNA associates with histones and other cellular and viral proteins (predominantly HBc and HBx). cccDNA complexes are organized in minichromosomes that persist in the nucleus and are transmitted to daughter cells.

Hepatitis B remains a major worldwide public health problem with around 260 million of chronically-infected people despite extensive vaccination programs. Chronic hepatitis B evolves towards life threatening complications including liver cirrhosis and cancer. Current therapeutic regimen (polymerase inhibitors and pegylated interferons) are long life treatment and fail to cure HBV as they do not target the virus reservoir. HBV functional cure remains a major unmet medical need.

ENYO Pharma lead candidate, Vonafexor (EYP001), is an orally bioavailable small molecule currently evaluated in phase IIa clinical trials, in patients with chronic hepatitis B. Vonafexor (EYP001) is a synthetic non-steroidal, non-bile acid FXR agonist with a good tolerability profile. Contrary to lifelong standards of care that target essentially virus replication, Vonafexor (EYP001) is notably targeting the cccDNA (‘virus reservoir’) therefore aiming for HBV cure. Strong, clinically significant decline of the HBsAg levels emerges in the majority of patients when reaching week 16 of the combination treatment of Vonafexor with pegylated Interferon, with and without Entecavir. Patients are monitored during additional 24 weeks to collect follow up data and to assess the HBsAg loss and functional cure rate.

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