Cambridge Healthtech Institute's Fifth Annual
HCV Drug Discovery
April 18-19 

Day 1 | Day 2
Download Drug Discovery Chemistry Brochure or HCV Drug Discovery Brochure

The newest therapies in more than a decade for people infected with the Hepatitis C virus (HCV) have recently hit the market. Hear about the chemistry of this new class of protease inhibitors and progress on 2nd generation versions, as well as updates on the clinical progress and chemical optimizations of other direct acting antivirals (DAAs). An emphasis will be on progress of various combinations of the new DAAs, especially in the context of an ideal interferon-free regimen. Newer anti-HCV drug candidates, including those that target host/virus interactions will also be covered.

WEDNESDAY, APRIL 18

12:30 pm Registration

 

TARGETING HOST/VIRAL INTERACTIONS

1:30 Chairperson’s Opening Remarks

Kai Lin, Ph.D., Group Head, Virology, Novartis

1:40 Update on HCV Entry Pathways and Targets for Therapeutic Intervention

Helen Harris, Ph.D., Senior Post-doctoral Fellow, Molecular Virology, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, UK

2:10 Novel Antiviral Preventive and Therapeutic Strategies Targeting Hepatitis C Virus Entry

Mirjam Zeisel, Ph.D., Pharm.D., Group Leader and Research Associate, Infectious Diseases, University of Strasbourg

Using a functional RNAi kinase screen we have recently identified a network of receptor tyrosine kinases (RTKs) as HCV entry factors. Functional studies demonstrate that kinases act on postbinding steps by interfering with CD81-claudin-1 co-receptor associations and membrane fusion. Using HCV cell culture and animal models models, we targeted host entry factors by receptor-specific monoclonal antibodies or inhibition of RTKs by approved protein kinase inhibitors. Entry and infection of all HCV genotypes was blocked including viral escape variants that are resistant to autologous host immune responses.

2:40 Discovery and Characterization of a Class of Small Molecule HCV Entry Inhibitors

Carl J. Baldick, Ph.D., Senior Research Investigator, Infectious Diseases Research and Development, Bristol-Myers Squibb

HCV entry is a multistep process mediated by viral envelope proteins E1 and E2, as well as several host cell factors.  A high throughput screen utilizing HCV pseudoparticles was used to identify a potent and selective class of triazine entry inhibitors.  Further development resulted in molecules with picomolar anti-HCV EC50 activities, and biological characterization demonstrates the potential value of inhibitors that target this stage of HCV infection.


3:10 Update on Development of Cyclophilin Inhibitor(s) for Combating HCV

Kai Lin, Ph.D., Group Head, Virology, Novartis

3:40 Networking Refreshment Break in Exhibit Hall with Poster Viewing

 

TOWARDS AN ALL ORAL REGIMEN

4:20 Combination DAA Strategies to Cure HCV

Xiao-Jian Zhou, Ph.D., Executive Director, Clinical Pharmacology & Early Medical Development, Idenix

Idenix Pharmaceuticals currently has two HCV DAAs in clinical development; IDX184, a nucleotide prodrug, and IDX719, an NS5A inhibitor, and has an ongoing HCV drug discovery program in nucleotide prodrugs. Our discovery efforts on novel HCV nucleotide prodrugs have identified several interesting molecules (both purines and pyrimidines) that are under preclinical evaluation. We believe that nucleoside/tide drugs will be a key component of future DAA combination regimens due to their potent pan-genotypic antiviral activity, low mg QD dosing, high barrier to resistance and low potential for drug-drug interactions. We will discuss the potential use of our pan-genotypic DAAs in PegIFN-free combination regimens to cure HCV.

4:50 Drug Resistance in DAA Combination Treatment

Christy Hebner, Ph.D., Research Scientist II, Gilead Sciences

Recent clinical studies using combinations of direct acting antivirals (DAAs) show promise for the future of possible interferon-sparing regimens for the treatment of HCV, though the impact of drug resistance mutations on the long-term effectiveness of such combination therapies are just beginning to be understood. Using deep sequencing technologies the emergence, frequency, and diversity of drug resistance mutations at early timepoints in monotherapy and combination therapy can be compared and the influence of detectable mutations on combination treatment outcomes assessed. Furthermore, such data can shed additional light on anti-HCV compound mechanisms of action and also lend practical insight into which DAA combinations may be best utilized for future combination therapies.   

5:20 Breakout Discussions

During this interactive session, audience members join one of the breakout discussions listed below. Participants are encouraged to share examples from their work, vet ideas with peers and ask questions of them. Each breakout discussion is a relaxed, informal exchange of ideas amongst scientists and is not meant to be, in any way, a corporate or specific product discussion.

 

Topic 1: What will be the ‘Ideal’ HCV Regimen?

Moderator: Kai Lin, Ph.D., Group Head, Virology, Novartis


•Bye-bye interferon?
•What about ribarvirin?
•Fitting in new classes/combinations

Topic 2: New Targets and Approaches

Moderator: John McCauley, Ph.D., Senior Scientist, Infectious Diseases, Merck


•Vaccines
•Micro RNA?
•Cell culture and animal models ‘advances’

Topic 3: Pan-Genotypic HCV Inhibitors/Combinations: How Long to the Market?

Moderator: Carl J. Baldick, Ph.D., Senior Research Investigator, Infectious Diseases Research and Development, Bristol-Myers Squibb


•Are nucleoside analogs alone enough?
•How do we define “pan-genotype” coverage in vitro?
•Will the HCV replication error rate make it difficult to find conserved targets?
•A unique role for targeting cellular proteins required for entry/replication?

6:20 End of Day

6:30 – Evening Dinner Workshop: HCV and the Host Immune System
(see SC6, separate registration required)



Day 1 | Day 2
Download Drug Discovery Chemistry Brochure or HCV Drug Discovery Brochure