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TBA
Dinner Meeting |
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Topic: "From Bench to the Clinic: Discovering and Development
of Hepatitis C Virus Antivirals"
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Speaker: David Olsen, PhD
Authors: ¹David Olsen,* ¹Steve Carroll, ²Larry
Handt, ³Ken Koeplinger, ³Christine Fanzozi, ³Rena
Zhang, ¹Donald Graham, 4Malcolm
MacCoss, 4Nigel Liverton, 4John
McCauley, 4Michael Rudd, 4Joseph
Vacca, ¹Daria Hazuda, ¹Steven Ludmerer
Summary: Current therapies to treat hepatitis C virus (HCV)
infection consist of combinations of pegylated interferon- and
ribavirin which have significant side effects and are of limited
utility in patients infected with HCV genotype 1, the most prevalent
genotype in developed countries. Efforts to develop novel therapies
with enhanced efficacy and tolerability have focused on direct
antiviral agents targeting the virally encoded RNA polymerase, NS5B,
and protease, NS3/4A. To develop an understanding of PK/PD
relationships using an animal model of chronic infection,
HCV-infected chimpanzees were administered MK-0608, an inhibitor of
the HCV RNA polymerase, or MK-7009, a macrocyclic inhibitor of the
HCV NS3/4A protease, at differing dose levels, durations, or routes
of administration. Short-term administration of either MK-0608 or
MK-7009 to HCV-infected chimpanzees resulted in profound viral load
suppression. The results for MK-0608 indicated a steep PK/PD
relationship, with a 10-fold difference in dose resulting in a
10,000-fold difference in viral load suppression. Dose-dependent
differences in efficacy were also observed with MK-7009. Resistant
viral variants were detected in rebounding viral populations in
chimpanzees dosed with either compound. Over 3 logs of R155K variant
resistant to MK-7009 was detected predose and persisted as a
significant fraction of the circulating viral population far longer
after cessation of dosing than did an S282T variant resistant to
MK-0608, suggesting the R155K virus has a replication fitness
similar to wild-type virus. The results of these studies regarding
efficacy and potential for development of antiviral resistance have
informed the strategy for clinical development of the compounds.
Footnotes: ¹Antiviral Research (WP), ²Laboratory Animal
Research (WP), ³Drug Metabolism (WP), 4Medicinal
Chemistry
BIOGRAPHY: David Olsen, Ph.D. has an undergraduate chemistry degree
and trained as a biochemist at University of Maryland, College Park
MD. David completed postdoctoral research at the Max-Planck
Institute for Experimental Medicine (Göttingen, Germany) where
he utilized chemistry, molecular biology and biochemical techniques
to investigate structure/function of catalytic RNA. After completing
his postdoctoral training, David joined the Antiviral Department at
Merck in 1991.
David has more then 18 years of antiviral drug discovery and
development experience with 59 publications. His career interests
have focused on HIV-1 protease and reverse transcriptase and
hepatitis C protease and polymerase inhibitory mechanisms. His other
research interests include mechanisms of antiviral resistance and
enzyme-nucleic acid interaction studies. In 2007 and 2008 David
served as a Senior Director and Head of the Department of Antiviral
Research in West Point Pennsylvania. In 2009 he transitioned to
External Basic Research where he functions as the Site Lead for the
Infectious Disease franchise.
In this new role, David expanded his area of drug discovery
research to cover Merck's external research pipeline in the areas of
antibacterial, antifungal and antiviral research. His team is
responsible for directing a dozen programs based in China, Japan,
India and Russia.
Please join us for dinner. Advanced reservations recommended.
MEETING DATE: TBA
PLACE: Snuffy's Restaurant, Park & Mountain Ave (Route 22
East), Scotch Plains, NJ Telephone: 1-908-322-7726
TIME: 6:00 pm Networkng/Cash Bar, 6:30 pm Dinner, 7:30 pm
Presentation
REGISTRATION: $35 ACC&CE Members, $45 Non-members
CANCELLATIONS must be made 24 hrs in Advance or Be
Invoiced.
DIRECTIONS: See below
To RESERVE: Call 1-973-729-6671 or e-mail:
accce@chemconsult.org
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Snuffy's Restaurant
Park and Mountain Ave. (off Route 22)
Scotch Plains, NJ 07076
Tel: 1-908-322-7726 www.weddingsatpantagis.com
Route 22 East : (Scotch Plains, Berkeley Heights, Fanwood, New
Providence Exit) - Make a right turn at the exit (under overpass) and
then go straight on Park Avenue for about 100 yards. Snuffy's will be on
the right. Route 22 West : (Scotch Plains, Berkeley Heights, Fanwood,
New Providence Exit) - At the exit, make a right turn. At the traffic
light, make a left turn and take the overpass over Route 22. At the end
of the overpass, make a right onto Park Avenue. Snuffy's will be on the
right.
Garden State Parkway : (North and South) - Take Exit 140 from the
Garden State Parkway and follow the signs for Route 22 West. Once on
Route 22 West, follow the directions above.
Route 78 : (East and West) - Take Exit 41 from Route 78. Follow the
signs to Scotch Plains. This will put you onto Plainfield Avenue. Follow
Plainfield Avenue straight through the traffic light, where it becomes
Bonnie Burn Road. Follow Bonnie Burn Road to the next traffic light and
make a right turn (sign Scotch Plains/Newark). Follow the overpass over
Route 22(traffic may back up here). At the end of the overpass, make a
right onto Park Avenue. Snuffy's will be on the right.
New Jersey Turnpike : (North and South) - Take Exit 14 from the New
Jersey Turnpike and follow the signs to Route 78 West. Once on Route 78
West, follow the directions above. |
