Antiviral drug development is shifting its focus to hepatitis B virus (HBV) after the encouraging success of developing direct-acting antivirals against the hepatitis C virus. Both viruses cause liver disease and represent major global health problems that can lead to death from liver failure. Much of the research focuses on broadly applicable antiviral approaches that modulate the host’s immune system or other infection response processes. Host immunomodulatory strategies are also being applied for treating emerging viral diseases. Progress has also been made in several HBV-specific approaches such as RNAi to silence HBV gene production, or inhibit the virus’ capsid assembly, which are in early-stage clinical trials or may be soon. Join us at CHI's Antivirals: Targeting HBV and Beyond symposium to stay abreast of new drug  development in the HBV and broader infectious disease field and to share insights and strategies with fellow researchers.

Final Agenda

Tuesday, September 25

8:00 am Pre-Conference Symposia and Short Course Registration (Ballroom Foyer)

8:00 Morning Coffee (Ballroom Foyer)

TARGETING THE RNA AND PROTEINS OF HEPATITIS B VIRUS
Hampton

9:00 Welcome Remarks

Anjani Shah, PhD, Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Andrew Vaillant, PhD, CSO, Replicor, Inc.

9:15 KEYNOTE PRESENTATION: New Directions towards a Functional Cure for Chronic Hepatitis B

Jan Martin Berke, PhD, Principal Scientist, Hepatitis Discovery, Janssen Research & Development, Beerse, Belgium

While approximately 260 million individuals worldwide are chronicall infected with the Hepatitis B virus, current regimens provide only a fraction of patients with functional cure, loss of S-antigen and suppression of the virus in the absence of continued treatment. With the goal of developing finite duration combination regimens that deliver a higher rate of functional cure, multiple mechanism of action agents are currently in development. This presentation will overview progress to date in this area.

9:45 Antiviral Activities of AB-506, a Next Generation HBV Capsid Inhibitor, in Combination with AB-452, an HBV RNA Destabilizer, Nucleos(t)ide Analogs and the RNAi Agent ARB-1467

René Rijnbrand, PhD, Vice President, Biology, Arbutus Biopharma Inc.

Increasing HBV cure rates will require a combination regimen that blocks viral replication, reduce s antigen levels, starve cccDNA formation and activate immune responses to eliminate cccDNA. Capsid inhibitor AB-506 in combination with RNA destabilizer AB-452, NAs or the RNAi agent ARB-1467 using HBV cell culture and animal models showed additive to synergistic antiviral activity. These data suggest that these agents are mechanistically compatible and may be used for treatment in a combination regimen.

10:15 Preclinical Antiviral Profile of the Novel HBV Core Inhibitor EP-027367

Michael Vaine, PhD, Principal Scientist, Virology, Enanta Pharmaceuticals

EP-027367 is a novel HBV inhibitor that modulates capsid assembly and other core protein functions. In vitro, it inhibits rcDNA production with low double digit nanomolar activity, is active across HBV genotypes A-H, nucleos(t)ide resistant variants, and inhibits nascent cccDNA formation in infectable cell lines. In a human liver, chimeric mouse model, EP-027367 can reduce circulating HBV titers by up to 3-logs with 28 days of treatment.

10:45 Networking Coffee Break with Poster Viewing (Foyer)

DIRECT-ACTING ANTIVIRALS FOR HBV
Hampton

11:30 AB-452: A Selective Small-Molecule Destabilizer of HBV Viral RNA

Min Gao, PhD, Senior Research Fellow, Arbutus Biopharma, Inc.

AB-452 is a potent HBV RNA destabilizer. It is inactive against a panel of DNA and RNA viruses, demonstrating the specificity of AB-452. Since AB-452 promotes the degradation of HBV RNAs, especially sRNA and consequently, inhibits multiple stages of viral life cycle in vitro and in vivo, combination regimens containing AB-452 could not only further inhibit HBV DNA replication and potentially increase the cure rate, but also provide an opportunity to shorten the treatment duration.

12:00 pm Using siRNA to Target the HBV Transcriptome

James C. Hamilton, MD, MBA, Vice President Clinical Development, Arrowhead Pharmaceuticals

Hepatocyte targeted siRNA therapeutics can be used to silence HBV viral mRNA transcripts leading to reduction in serum antigen levels and inhibition of viral replication. This mRNA silencing effect applies to the entire viral transcriptome including transcripts derived from integrated DNA and cccDNA which may be important in generating functional cures

12:30 HBV Ribonuclease H: Drug Discovery and Target Validation

John Tavis, PhD, Professor of Molecular Virology, Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine

HBV replication requires the viral ribonuclease H (RNaseH), but no anti-RNaseH drugs exist. We developed assays to measure RNaseH activity and identify HBV replication inhibitors. >100 inhibitors were found, the best having an EC50 of 110 nM and a therapeutic index of 390. RNaseH inhibitors are synergistic with nucleos(t)ide analogs, insensitive to HBV’s genetic diversity, and can suppress HBV viremia in infected humanized mice, so the RNaseH is a promising target for novel drug development.

1:00 Pre-Conference Short Course Registration (Ballroom Foyer)

1:15 Enjoy Lunch on Your Own

STIMULATING HOST RESPONSES AND TARGETING EMERGING VIRUSES
Hampton

2:45 Chairperson’s Remarks

René Rijnbrand, PhD, Vice President, Biology, Arbutus Biopharma Inc.

2:55 Achieving Functional Cure of Chronic HBV Infection with REP 2139-Based Combination Therapy

Andrew Vaillant, PhD, CSO, Replicor, Inc.

HBsAg loss during treatment of chronic HBV infection predicts functional remission persisting after the completion of therapy but is rarely achieved with approved therapies. REP 2139 uniquely allows HBsAg clearance in most patients, dramatically potentiating the ability of immunotherapy to restore host control of infection. Follow-up data from the latest clinical trials with REP 2139-based combination therapy demonstrating the achievement of long term functional cure in HBV and HDV infection will be featured.

3:25 Targeting TLR7 for Emerging Infectious Diseases

James B. Whitney, PhD, Professor, Center for Virology and Vaccine Research, Harvard Medical School and Ragon Institute of MGH, MIT, and Harvard

3:55 Small Molecule Inhibitors of Flavivirus Entry Inspired by the Humural Immune Response

Priscilla L. Yang, PhD, Professor, Department of Microbiology and Immunobiology, Harvard Medical School

Dengue virus is a pathogen of high biomedical significance against which we lack countermeasures. We have developed small molecules that bind to a conserved pocket on the dengue envelope protein and shown that these potently inhibit dengue, Zika, and related viruses by inhibiting membrane fusion during viral entry. These compounds mimic the activity of antibodies by engaging the envelope protein extracellularly but do so without the risk of antibody-dependent enhancement of infection and disease.

4:25 Closing Comments

4:30 Close of Symposium 

5:00 Pre-Conference Dinner Short Course Registration (Ballroom Foyer)