Dr. Stephan Urban: 2023 Baruch S. Blumberg Prize Recipient Seminar

This presentation was given on March 10, 2023 at the Hepatitis B Foundation by Dr. Stephan Urban, who was awarded the prestigious Baruch S. Blumberg Prize the same evening. Dr. Stephan Urban, head of the Translational Virology Unit at the Department of Infectious Diseases at Heidelberg University Hospital and Project Coordinator in the German Center for Infection Research, TTU Hepatitis. Dr. Urban and his team developed the first commercially available and approved drug for hepatitis delta, known as bulevirtide, and he will shed light on the journey of this discovery and how this tremendous medical breakthrough was achieved. Some questions that were asked and we didn't get to during the presentation are answered below: 1. Can you help me understand the interaction and its function between the Mycludex B and NTCP? Myrcludex B (Hepcludex/bulevirtide) binds with very high affinity to NTCP, the receptor of HBV and HDV and prevents the virus from being uptaken into the liver cell. Consequently cells, that are not infected (e.g. those that are newly formed or regenerate) are protected against becoming infection. With time infected cells get lost. The binding of myrcludex also inhibits the natural function of NTCP (bile acid transport). But this occurs only at very high concentrations and so far has no clinical consequences. 2. Remarkable synergy of IFN and MyrB. Have you shown the T-cell response in patient showing HBsAg seroconversion? I agree regarding the remarkable responses. Since we did not expect such dramatic immunological reactions , we did not implement the analysis of T-cell responses in the clinical trial at the time of setting up the trial. However, this is implemented in the follow up studies of the combination treatment. The data will be presented as soon as they are available. 3. In patients who did not show serum HBsAg reduction during Myr treatment, did you check cccDNA levels in the liver? This is an important question. Unfortunately, this analyses were not done in the Myr 202 study. But there will be a limited analyses of data available in the 301 study, which will probably be presented at the next EASL meeting. From the mode of action of the drug we would expect a reduction of cccDNA levels in the liver. The fact that HBsAg is not declining during treatment may be due to the source of HBsAg coming mostly from integrates in these HBeAg negative patients. Learn more about Hepatitis B and the Hepatitis B Foundation: hepb.org