Inaugural Symposium

Antivirals: Small Molecule Inhibitors of Viral Targets

Developing New Treatments for HBV and Other Viral Infections

April 22, 2016

Antivirals: Small Molecules against Viral and Host Targets Track 

This one-day symposium focuses on the medicinal chemistry behind the new small molecule and other types of potentially orally bioavailable drug candidates in development against Hepatitis B Virus (HBV) and a few other viruses actively being pursued in the drug development industry. Coverage will also include updates and reviews of broad spectrum approaches to develop single treatments against several types of viruses by targeting host immune responses. Brief clinical updates and reviews of the relevant infectious disease agents will be a part of the agenda as well. 

Final Agenda

Friday, April 22

8:00 am Registration and Morning Coffee


8:30 Chairperson’s Opening Remarks

David Smith, Ph.D., Vice President, Global Research and Development Leader, Hepatitis, Alios BioPharma, Inc., a Janssen Pharmaceutical Company of Johnson & Johnson

8:40 FEATURED PRESENTATION: Overview of Hepatitis B Virus Infection and Medical Landscape

Robert_GishRobert Gish, M.D., President, Robert G. Gish Consultants, LLC

This presentation will cover the hepatitis B life cycle, as a virus and in humans. The epidemiology of infection will also be presented. Promising future treatments and challenges will be highlighted.

9:25 Development of Combination Therapies for HBV

Michael_SofiaMichael J. Sofia, Ph.D., CSO, Arbutus Biopharma Inc.

Developing a cure for HBV is hindered by the ability of the virus to control and suppress the host immune response to infection and a reservoir of viral cccDNA. A therapeutic regimen that simultaneously controls viral replication, reactivates the host immune response and addresses the viral reservoir by combining drugs with different mechanisms of action has the potential to deliver an HBV cure. This presentation addresses the concept of combination therapy as a strategy for delivering a cure for HBV infection.

9:55 Coffee Break in the Exhibit Hall with Poster Viewing

10:35 Nucleic Acid Polymers: Antiviral Mechanisms and Application in the Treatment of Chronic HBV and HBV / HDV Infection

Andrew_VaillantAndrew Vaillant, Ph.D., CSO, Replicor Inc.

Nucleic acid polymers (NAPs) are a newly emerging antiviral technology for the treatment of chronic HBV infection and HBV / HDV co-infection. NAPs have the unique ability to clear HBsAg from the blood of human patients, a critical step in achieving a functional cure in HBV and HBV / HDV infection. Replicor will present its current mechanistic data underlying the basis for this unique antiviral effect of NAPs as well as updated clinical data showing Replicor’s progress in using NAP-based combination therapy in patients with chronic HBV infection and HBV / HDV co-infection towards achieving functional cure for these infections.

11:05 RSV Therapeutics: Drug Design and Clinical Development

Jerome Deval, Ph.D., Scientific Director, Biochemistry, Alios BioPharma

Matthew_McClureMatthew W. McClure, M.D., Senior Medical Director, Alios BioPharma, Inc., a Janssen Pharmaceutical Company of J&J

Respiratory syncytial virus (RSV) is a seasonal virus that causes serious morbidity and mortality, yet no effective vaccine or treatment exists. The drug development paradigm, including medicinal chemistry and biochemical approaches, that led to the discovery and selection of the RSV therapeutic ALS-008176 will be discussed. The regulatory and clinical challenges in developing a drug targeting RSV, particularly in an infant population, will then be highlighted.

11:35 Discovery of a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus

Sandrine_VendevilleSandrine Vendeville, Pharm.D., Ph.D., Senior Principal Scientist, Medicinal Chemistry, Janssen Infectious Diseases (Johnson & Johnson), Belgium

Optimization of a benzimidazole-based chemotype led to a new series of potent and orally bioavailable inhibitors of the fusion protein of RSV (Respiratory syncytial virus), a clinically validated target. This talk will be the first disclosure of the medchem optimization strategy, leading to the selection of JNJ-63718678, a picomolar inhibitor, having demonstrated good efficacy and tolerability in a human challenge study upon oral QD dosing. New insights on the mechanism of action and binding of this class of inhibitors will also be presented.

12:05 pm Sponsored Presentation (Opportunity Available)

12:20 Enjoy Lunch on Your Own


1:35 Chairperson’s Remarks

Michael J. Sofia, Ph.D., CSO, Arbutus Biopharma Inc.

1:40 Exploiting Apoptosis to Control Intracellular Infectious Agents: Development of Birinapant

Glenn_BegleyC. Glenn Begley, Ph.D., CSO, TetraLogic Pharmaceuticals

Avoidance of cell death is important in both infectious diseases and cancer, where the Inhibitor of Apoptosis (or IAP) proteins are key. The endogenous inhibitor of IAPs is SMAC, and birinapant is a SMAC-mimetic currently in phase 2 oncology trials. In a mouse model of hepatitis B virus (HBV), birinapant caused loss of HBV-DNA, loss of HBsAg, appearance of anti-HBsAg antibodies, and cooperated with the anti-viral entecavir. Birinapant will now be studied in HBV patients.

2:10 CPI-431-32, a Novel Cyclophilin Inhibitor for the Treatment of HBV

Robert_T_FosterRobert T. Foster, Pharm.D., Ph.D., CEO, Ciclofilin Pharmaceuticals Inc.

Cyclophilins are host proteins that play critical roles in the life cycles of HBV and other viruses. CPI-431-32 is a synthetic derivative of cyclosporin A that potently inhibits cyclophilins and blocks multiple HBV activities in vitro: cellular entry, DNA replication, HBeAg and HBsAg production, and generation of cccDNA. Oral administration of CPI-431-32 to HBV transgenic mice reduces HBV replication. CPI-431-32 also demonstrates anti-fibrotic activity in a NASH model. Investigations are underway to further characterize mechanisms of action.

2:40 CMX157, a Novel, Liver-Targeted, Tenofovir Prodrug, for the Treatment of Chronic HBV Infection

John Sullivan-Bólyai, M.D., CMO, ContraVir Pharmaceuticals Inc.

CMX157 is a novel, liver-targeted, lipid conjugate prodrug of tenofovir (TFV) designed to utilize natural lipid uptake pathways to achieve high hepatocellular levels of the active antiviral. Greater than 60 fold potency vs. TFV, high plasma stability and high first-pass liver extraction are expected to result in low clinical doses, anchoring single pill antiviral combinations, decreasing circulating TFV and off-target TFV toxicities, particularly to bone and kidneys, compared to the currently licensed TFV prodrug.

3:10 Refreshment Break in the Exhibit Hall with Poster Viewing

3:40 Host-Based Serine Protease Inhibitors as an Emerging Treatment against Influenza

Eric_MarsaultEric Marsault, Ph.D., Professor, Medicinal Chemistry and Pharmacology, University of Sherbrooke

Influenza is a leading cause of hospitalization and death, and occasionally the source of pandemics. Besides vaccination, current treatments target viral proteins and are associated with increasing resistance. Proteolytic cleavage of the virus hemagglutinin by host cell proteases is a pivotal early step of infectivity. We present herein potent and selective inhibitors of type 2 transmembrane serine proteases. Their efficacy and selectivity in vitro their ability to reduce virus replication of H1 and H3 subtypes in human epithelial respiratory cells (Calu-3) as well as their efficacy in vivo will be presented.

4:10 Broad-Spectrum Antiviral Agent: SB 9200 - a Potent, Novel Nucleotide Compound that Activates and Induces Intracellular Viral Sensors

Radhakrishna_IyerRadhakrishnan P. Iyer, Ph.D., CSO, Spring Bank Pharmaceuticals

Compounds that activate pathogen recognition receptors (PRRs) such as RIG-I, NOD2, STING etc., are of immense interest for the development of new generation antiviral agents. We have discovered SB 9200 as an oral broad-spectrum antiviral that activates RIG-I and NOD2 thereby causing the induction of expression of intracellular Interferons and ISGs. SB 9200 is being advanced into Phase II clinical trials against HBV, and RSV following successful completion of Phase I clinical trials in HCV-infected patients.

4:40 Close of Symposium