2017 Archived Content
Hepatitis B is a viral infection of the liver that is a major global health problem and can lead to death from liver fibrosis or liver cancer. The current treatments of daily nucleoside inhibitors only work in half the population and interferon, the other main treatment, has significant side effects making chronic usage difficult. However, the future of potential new treatments for HBV looks promising. Spurred by the recent success in developing direct acting antivirals that in combination have been able to cure hepatitis C, the antiviral drug development industry has re-focused its attention on HBV. However HBV has a few unique challenges such its covalently closed circular (ccc) DNA that is very resistant to destruction and can lead to ‘reservoirs’ of the virus remaining in treated cells. Join fellow infection disease researchers at Cambridge Healthtech Institute’s Inaugural Targeting HBV symposium to learn the latest and discuss the ‘behind the scenes’ medicinal chemistry and discovery innovations that are enabling progress.
Final Agenda
Monday, September 25
7:00 am Registration Open and Morning Coffee
7:55 Welcome Remarks
Anjani Shah, Ph.D., Conference Director, Cambridge Healthtech Institute
8:00 Chairperson’s Opening Remarks
Richard Colonno, Ph.D., CSO, Assembly Biosciences
8:10 Targeting HBV Surface Antigen with Nucleic Acid Polymers (NAPs): Updates on Pharmacology, Toxicity and Achieving Functional Cure of HBV and HDV Infection
Andrew Vaillant, Ph.D., CSO, Replicor Inc.
NAPs have a unique ability to eliminate circulating HBsAg, potentiating the ability of immunotherapy to achieve functional control of HBV and HDV infection. Recent breakthroughs in modeling NAP effects in vitro and updated pre-clinical and clinical data continue to advance the understanding of how NAPs work and their clinical impact against HBV and HDV infection.
8:40 HBV Capsid Assembly Inhibitors
Rene Rijnbrand, Ph.D., Vice President, Biology, Arbutus
AB-423 is an HBV capsid inhibitor that has shown in vitro and in vivo antiviral activity. AB-423 has been shown to impact the HBV life cycle at two distinct stages: the formation of novel core particles, required for the formation of rcDNA, and the unpacking of the rcDNA from these particles, required for cccDNA formation. AB-423 acts additively to synergistically with siRNA and nucleoside inhibitors.
9:10 Targeting HBV Core Protein to Achieve Higher Cure Rates
Richard Colonno, Ph.D., CSO, Assembly Biosciences
With HBV cure rates below 5%, additional novel therapies are needed. HBV Core protein (Cp) plays a critical role in multiple steps related to the generation of cccDNA, a key viral moiety responsible for infection and maintenance of chronic infection. We are developing a series of novel CpAMs (Cp Allosteric Modifiers) that target Cp and reduce cccDNA levels in infected cells via multiple mechanisms.
9:40 Networking Coffee Break with Poster Viewing
10:10 RNAi Interference: A New Tool in the Toolbox for Treatment of HBV
Amy Lee, Ph.D., Senior Director, In vivo Pharmacology, Arbutus
ARB-1467 and ARB-1740 are RNAi therapeutics currently in Phase II MAD clinical studies. These agents are designed to inhibit viral replication, cleave HBV transcripts, and lower all viral antigens. Reducing HBV proteins, particularly HBsAg, is expected to abrogate viral suppression of immune function and facilitate reinvigoration of the host response/defense. Preclinical studies suggest that combination of RNAi with standard-of-care drugs can enhance control of HBV.
10:40 RNAi in HBV, the Next Backbone Therapy for Use in Combinations?
Bruce Given, M.D., COO, Head of R&D, Arrowhead Pharmaceuticals
Arrowhead was the first broadly used RNAi studied in HBV. Based on our experience in treatment of naïve and experienced patients, we believe that RNAi will become a backbone therapy, together with NUCs, in the next generation of combination therapies seeking functional cure.
11:10 Sponsored Presentation (Opportunity Available)
11:40 Enjoy Lunch on Your Own
1:10 pm Chairperson’s Remarks
Rene Rijnbrand, Ph.D., Vice President, Biology, Arbutus
1:20 KEYNOTE PRESENTATION: Targeting HBV: Integrating Approaches
Pierre Raboisson, Ph.D., Head, IDV Europe Discovery, Janssen
1:50 CANCELLED: Entry Inhibition as a Therapeutic Concept for the Treatment of Hepatitis B and D Virus Infections
Stephan Urban, Ph.D., Professor, Department of Infectious Diseases, Translational Virology, University Hospital Heidelberg
Entry inhibition is an interesting, potentially curative opportunity to treat viral infections. The development of Myrcludex B as a potent inhibitor of the HBV/HDV receptor NTCP opened a novel therapeutic option to treat chronically infected patients. In my talk, I will discuss the current state of the art of entry inhibition for HBV/HDV and discuss, if such strategies might become important for future therapeutic regiments.
2:20 Targeting HBx and Smc5/6 Interactions
Dara Burdette, Ph.D., Research Scientist II, Discovery Virology, Gilead Sciences
The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing X protein (HBx), which targets Smc5/6 for degradation shortly after HBV infection. While the mechanism of transcriptional suppression remains to be elucidated, our data indicate that Smc5/6 restricts HBV when localized to ND10 and without inducing an innate immune response.
2:50 Networking Refreshment Break with Poster Viewing
3:30 Achieving Functional Cure in HBV: The Dinucleotide SB 9200 as an Immuno-Modulatory Anti-HBV Agent
R. P. (Kris) Iyer, Ph.D., Co-Founder and CSO, Spring Bank Pharmaceuticals, Inc.
Over 350 million people worldwide are infected with chronic hepatitis B (CHB). While life-long therapy with direct-acting nucleoside and nucleotide antivirals (DAAs) effectively suppress viral replication, development of resistance and toxicity to DAAs remain a significant problem. In CHB, the cellular innate and adaptive immune responses critical for antiviral defense are disabled. SB 9200, a novel synthetic dinucleotide, activates cellular viral sensors RIG-I and NOD2, restores the production of IFNs, ISGs and antiviral cytokines, and shows potent in vitro and in vivo antiviral activity. SB 9200 is being currently evaluated both as a monotherapy and in combination with Viread® in global Phase II clinical trials.
4:00 CRV431: Exploring the Cyclophilin Inhibitor Mode of Action in HBV
Robert T. Foster, PharmD, Ph.D., CSO, ContraVir Pharmaceuticals Inc. and Professor, Pharmacy & Pharmaceutical Sciences, University of Alberta, Canada
CRV431 is a proprietary host targeting cyclophilin inhibitor designed for the treatment of hepatitis B viral infection. The detailed mode of action of CRV431 is being examined and has thus far been shown to abrogate binding between cyclophilin A and two important viral proteins, HBsAg and HBx. These proteins play a vital role in the pathogenesis of infection and the propagation of liver disease.
4:30 Therapeutic Development for HIV and Emerging Diseases: Targeting TLR7 and other Approaches
James B. Whitney, Ph.D., Assistant Professor, Harvard Medical School, the Ragon Institute of MGH, MIT, and Harvard and the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center
5:00 Close of Symposium
5:00 Pre-Conference Dinner Short Course Registration
Click here for details on short courses offered.