Cambridge Healthtech Institute's Fifth Annual
HCV Drug Discovery
April 18-19
Day 1 | Day 2 | Download 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
1:30 Chairperson’s Opening Remarks
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
Thomas F. Baumert, M.D., Professor, 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 Sponsored Presentations (Opportunity Available)
3:40 Networking Refreshment Break in Exhibit Hall with Poster Viewing
4:20 Combination DAA Strategies to Cure HCV
David Standring, Ph.D. or colleague, Idenix
Idenix Pharmaceuticals currently has two HCV DAAs in clinical development; IDX184, a nucleotide prodrug and IDX375, a non-nucleoside polymerase inhibitor, and has ongoing HCV drug discovery/development programs in nucleotide prodrugs, protease inhibitors and NS5A inhibitors. Our discovery efforts on novel HCV nucleotide prodrugs have identified several interesting molecules (both purines and pyrimidines) that are under (delete intensive) 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
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 Brochure