EYP001 in HBV

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 over 350 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, EYP001, is an orally bioavailable small molecule currently evaluated in phase Ib in patients with chronic hepatitis B. A Phase IIa is planned to start in H2 2018. 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, EYP001 is targeting the cccDNA (‘virus reservoir’) therefore aiming for HBV real cure.

Key Opinion Leaders

Robert G. Gish, MD

Dr Gish obtained his medical degree from the University of Kansas Medical School in Kansas City, Kansas. He completed a 3-year internal medicine residency at the University of California, San Diego, and a 4-year gastroenterology and hepatology fellowship at the University of California, Los Angeles.

Dr Gish is a fellow of both the American College of Physicians and the American Association for the Study of Liver Disease. He has served on the editorial boards of American Journal of Gastroenterology, Journal of Hepatology, Digestive Diseases and Sciences, and Gastroenterology, among others. He has co-authored a public health policy for liver health in Vietnam and is also assisting with the development of health care policies in Armenia and the Philippines. He was a major early contributor to decipherment methods for the detection of hepatitis B and C virus and characterizing its epidemiology and clinical presentation in humans. He was involved in studies that led to the genotypic classification strategies and methods now in use worldwide. He has published more than 600 original articles, review articles, abstracts, and book chapters.

Robert G. Gish, MD, is currently an Adjunct Professor of Medicine at Stanford University in Palo Alto and an Adjunct Professor of Medicine at the University of Nevada School of Medicine in Las Vegas. In addition, he is also the Medical Director of the Hepatitis B Foundation and Medical Director of the Asian Pacific Health Foundation.

Hendrik W. Reesink, MD, PhD

Associate Professor in the Department of Gastroenterology and Hepatology and Experimental Immunology of the Academic Medical Center, University of Amsterdam, The Netherlands.

After receiving his medical degree from the Faculty of Medicine of the University of Amsterdam The Netherlands, he specialised in immuno-hematology and transfusion medicine at the Central Laboratory of The Netherlands Blood Transfusion Service, linked to the University of Amsterdam and subsequently he got his training in internal medicine at the Wilhelmina Gasthuis, of the University of Amsterdam. He also received a PhD degree from that institution.
He was the director of the Blood Bank in Amsterdam for almost 30 years and worked as general internist at the Onze Lieve Vrouwe Gasthuis in Amsterdam for more than 25 years. He works since 2004 exclusively as internist/ hepatologist in the Academic Medical Center departments of Gastroenterology and Hepatology and Experimental Immunology with special focus on viral hepatitis B and C research.

He is a member of numerous research groups and national and international advisory boards. He is the (co) author of numerous publications that have appeared in such journals as New England Journal of Medicine, The Lancet, Gastroenterology and Hepatology.