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Potential for a new Treatment Paradigm
Cell culture studies repeatedly demonstrate viral extinction following exposure to KP-1461. Whether this effect
will also be seen in humans is the subject of ongoing clinical trails. Should KP-1461 lead to viral collapse
in humans, the treatment paradigms for HIV will inalterably change. No longer will HIV therapeutics focus on
life-long inhibition of viral growth as their goal, but rather on the possibility of achieving viral eradication.
The progressive accumulation of such errors leads to degraded
viral fitness, loss of viability, and the eventual collapse of the viral
KP-1461 Demonstrates Viral Eradication in Vitro
population. This has been confirmed by in vitro experiments
which demonstrate irreversible viral extinction. Among the more
10000.0
than twenty approved antiretroviral agents, extinction of HIV in
1000.0
vitro is unique to KP-1461.
100.0
The Development of Viral Decay Acceleration
10.0
The complex and dynamic nature of viruses has been described
HIV P24 (ng/mL)
in the "quasispecies" model introduced by German biophysicist
1.0
and Nobel laureate Manfred Eigen. Eigen shed new light on the
0.1
question of how viral populations, particularly those composed
of mutated variants adapt and persist.
0.0
12345 6 78910 11 12 13 14
In discussing the framework of the quasispecies and why it has
Passage Number
readily adapted to conventional antiviral treatments, Eigen posit-
Harris et al. 2005, Antiviral Res. 67:129
ed an approach to “exploit their nature as a quasispecies and
thereby undermine the very basis of their existence.”
Koronis Pharmaceuticals
Utilizing the concepts introduced by Eigen, leading researchers
Koronis is a development stage, privately held company focused
Drs. Larry Loeb and Jim Mullins, both of the University of
on the efficient advancement of its clinical development efforts.
Washington, and John Essigmann at the Massachusetts Institute
In addition to KP-1461 for HIV, Koronis is also investigating the
of Technology developed Viral Decay Acceleration – an approach
application of VDA-based therapeutics for the treatment of hep-
designed to take full advantage of the natural adaptability and
atitis C and Respiratory Syncytial Virus (RSV). Preclinical pro-
variability of a virus in order to target its destruction. KP-1461, tar-
grams are currently underway and the Company is targeting to
geting HIV, is the first therapeutic developed from the VDA plat-
identify a preclinical candidate for HCV by the end of 2007. The
form technology. The VDA approach holds potential application
Company is actively exploring partnership opportunities for its
for several human viral diseases including hepatitis C.
VDA therapeutics.
KP-1461 Clinical Development
Selected Publications
KP-1461 is currently being studied in an open label, Phase 2a trial
Eigen, Manfred. Viral Quasispecies. Scientific American,July 1993.
to evaluate the safety, efficacy and tolerability when adminis-
tered as monotherapy in treatment-experienced patients. The
Smith, R, Loeb L., Preston B. Lethal Mutagenesis of HIV. Virus
study will enroll up to 32 individuals who harbor significant
Research. 2005; 105: 215-228.
resistance to conventional antiretroviral therapies. Patients will
receive 1600 mg of KP-1461 twice daily for 124 days. The study Harris, K., Brabant W., Styrchak S., Gall A., Daifuku, D.KP-1212/1461,
will be conducted at 30 academic and community-based clinical Anucleoside designed for the treatment of HIV by viral mutagen-
research centers in the United States. An independent Data esis. Antiviral Research 2005: 67(1-9).
Safety Monitoring Board will provide safety oversight.
Phase I studies performed in healthy volunteers and HIV-infected
individuals revealed that the drug was generally safe and well
tolerated.
KORONIS PHARMACEUTICALS 12277 134th Court NE, Suite 110 Redmond, WA 98052
www.koronispharma.com
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